Smoking, Nicotine and Pregnancy 3 Trial
| ISRCTN | ISRCTN84798566 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN84798566 |
| IRAS number | 291236 |
| Secondary identifying numbers | CPMS 49947, IRAS 291236 |
- Submission date
- 13/10/2021
- Registration date
- 13/10/2021
- Last edited
- 14/11/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Background and study aims
Nicotine replacement therapy (NRT) provides nicotine without the toxins contained in cigarette smoke. When used with specialist support, it helps pregnant women stop smoking. The NRT instruction booklet includes use for preloading, reduction and lapse recovery; studies suggest that allowing people to smoke and use NRT together helps with stopping. Currently, NHS stop smoking support advises pregnant women not to smoke when using NRT. This study will test whether relaxing this message could help pregnant women to quit and improve babies’ health. The aim of this study is to test support for the following three uses of NRT:
1. Preloading - using nicotine patches for a short time when still smoking but preparing to stop
2. NRT in ‘slip ups’ (smoking occasional cigarettes) – advice to keep on with NRT during short ‘slip ups’; this may help them stop smoking for good
3. For women who cannot quit, using NRT to smoke less – this could also help them stop smoking; if not, breathing in less harmful cigarette smoke should make babies healthier
Who can participate?
Pregnant women (pregnant for 25 weeks or less) who smoke
What does the study involve?
Participants will be randomly assigned into two groups. One group will receive usual NHS stop smoking support (counseling and NRT). The second group will also receive support with preloading NRT patches for up to 4 weeks before they try to quit and using NRT during ‘slip-ups’. Women who cannot stop after 6 weeks will receive support and an offer of NRT to help them to reduce their smoking. The researchers will collect saliva and breath samples before/during the study to measure nicotine and CO levels respectively. They will ask women about their smoking 6 weeks into the study and when they are 36 weeks pregnant. They will collect data on birth outcomes. Data will be compared between the two groups.
What are the possible benefits and risks of participating?
The researchers cannot promise that the study will directly benefit participants, but all participants will receive support to stop smoking based on the best NHS standards of practice. The information they provide during the study will be invaluable in helping the researchers design future ways of helping pregnant women stop smoking. The researchers do not foresee there being any risks from taking part in this study. However, taking part will take time and may therefore be inconvenient. Some participants may be upset when discussing the risks of smoking in pregnancy.
Where is the study run from?
University of Nottingham (UK)
When is the study starting and how long is it expected to run for?
April 2019 to October 2026
Who is funding the study?
National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (UK)
Who is the main contact?
Dr Katarzyna Campbell
kasia.campbell@nottingham.ac.uk
snap3-trial@nottingham.ac.uk
Contact information
Dr Katarzyna Campbell
Scientific
Scientific
Division of Primary Care, School of Medicine
University of Nottingham
Room 1407, Floor 14, Tower Building
Nottingham
NG7 2RD
United Kingdom
 ORCID ID |
0000-0001-7453-9138 |
|---|---|
| Phone | +44 (0) 115 74 84 508 |
| kasia.campbell@nottingham.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Education or Self-Management, Psychological & Behavioural |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Community, GP practice, Hospital, Internet/virtual, Other |
| Study type | Prevention |
| Participant information sheet | 40539_PIS_V1.0_25Aug21_Interview.pdf |
| Scientific title | Open-label randomized controlled trial of enhanced support and nicotine replacement therapy (NRT) offered for preloading, lapse recovery and smoking reduction: impact on smoking in pregnancy |
| Study acronym | SNAP 3 |
| Study hypothesis | To find out if additional support for preloading (using nicotine replacement therapy [NRT] patches in preparation for quit) and recovery of lapses ('slip ups' to smoking during quit attempt) and an offer of NRT for preloading, when added to usual care (UC), i.e. usual NHS smoking cessation support, increase pregnant women's chances of long term smoking cessation, compared to UC alone. |
| Ethics approval(s) | Approved 13/09/2021, West Midlands - Coventry and Warwickshire Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)207 104 8084; coventryandwarwick.rec@hra.nhs.uk), REC ref: 21/WM/0172 |
| Condition | Smoking in pregnancy |
| Intervention | Current interventions as of 21/11/2023: The study design is randomised control trial (RCT) recruiting from antenatal settings and via online recruitment. There will be two trial arms. The control arm will receive standard stop smoking cessation care available for pregnant women, which may include the provision of nicotine replacement therapy (NRT) during the quit attempt (UC group). The intervention arm participants, in addition to standard care, will receive behavioural support and NRT for preloading (using NRT to gradually reduce smoking, until they quit on their agreed quit date) and advice on using NRT in brief smoking lapses during the quit attempt. Women who are unable to quit 6 weeks post-randomisation will receive NRT and advice on using it to reduce smoking. Outcomes updated 15/12/2022 Protocol v 3.1 The researchers will compare the following between the intervention and the UC group: 1. Long-term abstinence from smoking reported between six weeks after randomisation and 36 weeks gestation or childbirth, whichever is earlier, confirmed by saliva and/or breath sample; 2. Reported and validated 7-day smoking abstinence at 36 weeks gestation 3. Reported ≥ 50% reduction in daily cigarettes at 36 weeks gestation 4. Exhaled CO concentration at delivery 5. Whether or not brief smoking lapse experienced, reported at 6 weeks post randomisation 6. Adverse pregnancy outcome rates(e.g. low birth weight for gestational age, premature birth) The researchers will recruit 1430 pregnant women who are ≤25 weeks gestation, smoke, are willing to use NRT and wish to receive support to stop smoking. They will ask the woman's GP to confirm there are no contraindications to NRT use. The researchers anticipate the recruitment will take 30 months. Participants will be recruited from approximately 8 weeks gestation. They will collect follow up data from participants at 6 weeks post-randomisation and at around 36 weeks gestation. They will collect birth and maternal outcome data from the hospital after birth, and no later than 10 weeks postpartum. Therefore, the maximum duration of the study for any participant would be approximately 42 weeks. Updated 15/12/2022 Protocol v3.1 Staff involved in the trial procedures will include: 1. Site trial staff: Clinical Research Network (CRN) staff, research nurses, research midwives or any local site staff delegated by the site PI 2. Central research team: smoking in pregnancy (SIP) researchers, SIP administrators or any staff delegated by the CI 1. Participant identification and screening: A screening questionnaire (paper or electronic) will be used in all settings to identify potentially eligible women. A paper or electronic copy of the patient information sheet (PIS) will be made available to women at this point. Those potentially eligible and interested will be asked to provide their contact details and will have the opportunity to discuss the study with a researcher. Participants will be identified in the following settings: 1. Antenatal hospital recruitment settings - face to face by the usual clinical care team. The care team may pre-identify potential participants and send them a letter or email with a screening questionnaire, PIS and consent form before their appointment. Alternatively, the care team or local site trial staff may approach women during appointments, introduce the study/offer PIS and ask women to complete the screening questionnaire. Posters will also be put in relevant clinical areas and women will be able to access the screening questionnaire and PIS via a link or by scanning a code on the poster. 2. Participant Identification Centres (PICs) in antenatal hospital settings and GP surgeries - the usual care team or site trial staff will identify potential participants as above and will pass their details to the central research team. 3. Community midwives may also refer potentially eligible and interested women to the central or local research teams, using the screening questionnaire. 4. Stop smoking practitioners may also refer potentially eligible and interested women to central or local research teams 5. Online adverts targeted towards pregnant women who smoke - women will be directed to a link to the PIS and screening questionnaire. Their details will be passed on to the central research team. Research team staff will contact women identified in PICs, by community midwives, stop smoking practitioners and online, to discuss the study in more detail. Recruitment: 1. Participants identified in hospital recruitment settings will discuss the study with site trial staff who will talk them through the PIS and answer any questions. Women who had the chance to fully understand the study and are happy to give their consent will be recruited during the appointment. Women who would like more time to decide will be contacted at least 24 hours later to further discuss their participation. The site trial staff will collect consent, either face to face or by telephone. 2. Participants identified in PICs, by community midwives and online will be contacted via telephone/video call by a central research team member, who will discuss the study with them. For those who do not recall receiving a PIS, a copy will be sent electronically at least 24 hours before consent. 2. Baseline appointment: Consent: Informed consent will be collected from all participants before any intervention or data collection. An Investigator or their delegate will go through the consent form with the potential participant, answer questions and obtain consent. Consent will be collected either face to face or using 'distanced' consent via telephone or video call. Women will be asked to tick or initial each consent item and sign the consent form, either using paper (face to face only) or electronic form (e-consent; face to face or distanced). When obtaining distanced consent, if e-consent is not possible (e.g. if there is no internet connection) verbal telephone consent will be obtained, following a strict scripted protocol, which will follow the same consent items as the 'hard copy' consent form. Eligibility will be formally confirmed once consent is collected. Very brief advice (VBA) for smoking cessation in pregnancy: As part of the baseline appointment, all women will receive VBA as defined by the National Centre for Smoking Cessation Training (NCSCT). This is part of standard care for smoking cessation in pregnancy. VBA comprises (1) carbon monoxide (CO) testing, (2) advice that intensive behavioural support enhances success with quitting and (3) referral for this, if available locally. Data collection at baseline: Participants will complete baseline measures, including demographics, smoking beliefs and behaviours and provide necessary details about the pregnancy/antenatal care. The baseline questionnaire will be completed verbally, either face to face or during a telephone/video call. Samples: Saliva/Breath samples may be collected, at the clinic appointment or by the participant. If sample collection in the clinic is not possible, we may post saliva sample kits and individual-use carbon monoxide (iCO) monitors, with instructions, may be sent to participants by post. Women will be asked to send the saliva sample via post in a pre-paid envelope. iCO monitor will be used with a mobile app, which will send the results to the central research team electronically. Saliva sample will only be collected from women recruited in clinic, and randomised to intervention group. Randomisation: Participants will be allocated into one of the two groups by chance, by the Investigator or delegate, using a randomisation website. Referral for stop smoking support: Once randomised, women in the UC group will be referred for standard stop smoking support available in their area at the end of their baseline appointment, as per standard care. Women in the intervention group will receive enhanced preloading telephone support (see below) and will be referred for UC smoking cessation support at the end of the preloading component of the intervention (at quit date, up to 4 weeks post-randomisation). 3. Post-randomisation study pack via post: All women will receive a study starter pack via post. For all women, this will contain: - a "What happens next" information sheet - a standard care information leaflet - if applicable, saliva sample kit(s) with instructions - if applicable, iCO monitor with instructions The intervention group will also receive - 1 week worth of NRT patches (15 mg/16 h), with instructions - a preloading information leaflet - an access to the study website, which will reiterate the information contained in the preloading booklet These resources will complement the advice provided during enhanced preloading telephone support. 4. Intervention (intervention group only) Preloading phase and NRT provision and advice on using NRT in brief lapses: - shortly after dispatch of the starter pack, central research team members will contact participants in the intervention group. They will receive up to 4 weekly telephone/video support calls delivered by a university researcher. The number of calls will depend on when the quit date is set up (e.g. if the quit date is set up in 1 week, participants will only receive the first call, at the end of which they will be referred for standard smoking cessation support). Call 1 - The researcher will explain how to use the NRT received in the starter pack for preloading. The use of NRT in brief smoking lapsed will also be discussed. The researcher will help women set a quit date, at least 1 week but no more than 4 weeks ahead. Calls 2-3 - The researcher will ask women how they got on with the NRT; reinforce preloading/brief lapse advice; more NRT will be issued if needed. Final call - During the final call before the quit date, the researcher will refer women for standard smoking cessation support in their area, as described above. Data collection - Preloading phase (Pilot only): During the first 9 months of the trial (in-trial pilot) saliva and/or CO sample will be collected from a sub-sample of women who use NRT for preloading. 5. Standard smoking cessation support which combines behavioural support and provision of NRT, will be offered to all participants (UC group - at baseline; intervention group - after preloading phase). Smoking cessation support varies in different areas. If no specialist services are available in an area, the researchers will refer women for cessation support to their GP/midwife. 6. Data collection - follow up (FU) 1 (6 weeks post-randomisation): An online questionnaire (approx. 10 minutes) including smoking behaviours since randomisation, NRT use and access to stop smoking services. If unable to collect data via an online questionnaire, the research team will attempt to obtain data via telephone, text message or post. 7. Intervention (intervention group only) Reduction phase - advice and NRT provision: Women who report smoking at FU1 will be contacted by the central team researcher via telephone and offered a re-referral for smoking cessation support. Those who refuse will be offered the reduction phase of the intervention. If they accept this, they will receive 2 weeks supply of NRT via post. The researcher will advise them to use NRT (patches and/or inhalators) daily and smoke less than usual. NRT will be repeated on demand unless the participant reports smoking more than at baseline or more than 10 cigarettes each day, for 2 consecutive weeks. They will also receive bi-weekly telephone/video call support and supportive text messages, until up to 36 weeks gestation. NicUse App - throughout the reduction phase, women will be instructed to report smoking and NRT/e-cigarette use via a smartphone application, daily. They will receive instructions, a link to the app and login details. This is for self-monitoring purposes. 8. Data collection - FU2, at 36 weeks gestation or at childbirth, whichever is soonest. An online questionnaire (approx. 10 minutes), including smoking behaviours, stop smoking support. If unable to collect data via an online questionnaire, the central research team will attempt to obtain data via telephone, text message or post. Data may be obtained by site trial staff during antenatal appointments. Validation of smoking status - women who report long term quit (between FU1 and FU2) or at least 50% smoking reduction, will be asked to provide saliva and/or breath sample (using methods as described at baseline) to confirm smoking status. 9. Maternal and birth outcomes - after birth (up to 10 weeks postpartum) we will request these data from the hospital or GP. 10. Interviews to improve recruitment (Pilot only): Potentially eligible women who provide contact details via screening questionnaire, both those who agree to participate in the trial and those who decline, will be invited to take part in a telephone interview, lasting approx. 40 minutes. They will be asked to discuss the factors that influenced their decision to join or not. Interviews will be audio recorded. Incentives: Women will be offered £5 shopping vouchers for completing each FU questionnaire. They will be offered a £20 voucher for saliva/CO samples (except baseline) and a £20 voucher for taking part in the interview. _____ Previous interventions from 08/03/2022 to 21/11/2023: The study design is randomised control trial (RCT) recruiting from antenatal settings and via online recruitment. There will be two trial arms. The control arm will receive standard stop smoking cessation care available for pregnant women, which may include the provision of nicotine replacement therapy (NRT) during the quit attempt (UC group). The intervention arm participants, in addition to standard care, will receive behavioural support and NRT for preloading (using NRT to gradually reduce smoking, until they quit on their agreed quit date) and advice on using NRT in brief smoking lapses during the quit attempt. Women who are unable to quit 6 weeks post-randomisation will receive NRT and advice on using it to reduce smoking. The researchers will compare the following between the intervention and the UC group: 1. Long-term abstinence from smoking reported between six weeks after randomisation and 36 weeks gestation or childbirth, whichever is earlier, confirmed by saliva and/or breath sample; 2. Reported 7-day smoking abstinence at 6 weeks after randomisation 3. Reported and validated 7-day smoking abstinence at 36 weeks gestation (or childbirth, if sooner) 4. Reported and validated ≥50% reduction in daily cigarettes at 36 weeks gestation 5. Exhaled CO concentration at delivery 6. Adverse pregnancy outcome rates(e.g. low birth weight for gestational age, premature birth) The researchers will recruit 1430 pregnant women who are ≤25 weeks gestation, smoke, are willing to use NRT and wish to receive support to stop smoking. They will ask the woman's GP to confirm there are no contraindications to NRT use. The researchers anticipate the recruitment will take 30 months. Participants will be recruited from approximately 8 weeks gestation. They will collect follow up data from participants at 6 weeks post-randomisation and at around 36 weeks gestation. They will collect birth and maternal outcome data from the hospital after birth, and no later than 10 weeks postpartum. Therefore, the maximum duration of the study for any participant would be approximately 42 weeks. Staff involved in the trial procedures will include: 1. Site trial staff: Clinical Research Network (CRN) staff, research nurses, research midwives or any local site staff delegated by the site PI 2. Central research team: smoking in pregnancy (SIP) researchers, SIP administrators or any staff delegated by the CI 1. Participant identification and screening: A screening questionnaire (paper or electronic) will be used in all settings to identify potentially eligible women. A paper or electronic copy of the patient information sheet (PIS) will be made available to women at this point. Those potentially eligible and interested will be asked to provide their contact details and will have the opportunity to discuss the study with a researcher. Participants will be identified in the following settings: 1. Antenatal hospital recruitment settings - face to face by the usual clinical care team. The care team may pre-identify potential participants and send them a letter or email with a screening questionnaire, PIS and consent form before their appointment. Alternatively, the care team or local site trial staff may approach women during appointments, introduce the study/offer PIS and ask women to complete the screening questionnaire. Posters will also be put in relevant clinical areas and women will be able to access the screening questionnaire and PIS via a link or by scanning a code on the poster. 2. Participant Identification Centres (PICs) in antenatal hospital settings - the usual care team or site trial staff will identify potential participants as above and will pass their details to the central research team. 3. Community midwives may also refer potentially eligible and interested women to the central or local research teams, using the screening questionnaire. 4. Stop smoking practitioners may also refer potentially eligible and interested women to central or local research teams 5. Online adverts targeted towards pregnant women who smoke - women will be directed to a link to the PIS and screening questionnaire. Their details will be passed on to the central research team. Research team staff will contact women identified in PICs, by community midwives, stop smoking practitioners and online, to discuss the study in more detail. (Note - currently the researchers have not identified any PIC sites, but we may include sites that wish to act as PICs in the future). Recruitment: 1. Participants identified in hospital recruitment settings will discuss the study with site trial staff who will talk them through the PIS and answer any questions. Women who had the chance to fully understand the study and are happy to give their consent will be recruited during the appointment. Women who would like more time to decide will be contacted at least 24 hours later to further discuss their participation. The site trial staff will collect consent, either face to face or by telephone. 2. Participants identified in PICs, by community midwives and online will be contacted via telephone/video call by a central research team member, who will discuss the study with them. For those who do not recall receiving a PIS, a copy will be sent electronically at least 24 hours before consent. 2. Baseline appointment: Consent: Informed consent will be collected from all participants before any intervention or data collection. An Investigator or their delegate will go through the consent form with the potential participant, answer questions and obtain consent. Consent will be collected either face to face or using 'distanced' consent via telephone or video call. Women will be asked to tick or initial each consent item and sign the consent form, either using paper (face to face only) or electronic form (e-consent; face to face or distanced). When obtaining distanced consent, if e-consent is not possible (e.g. if there is no internet connection) verbal telephone consent will be obtained, following a strict scripted protocol, which will follow the same consent items as the 'hard copy' consent form. Eligibility will be formally confirmed once consent is collected. Very brief advice (VBA) for smoking cessation in pregnancy: As part of the baseline appointment, all women will receive VBA as defined by the National Centre for Smoking Cessation Training (NCSCT). This is part of standard care for smoking cessation in pregnancy. VBA comprises (1) carbon monoxide (CO) testing, (2) advice that intensive behavioural support enhances success with quitting and (3) referral for this, if available locally. Data collection at baseline: Participants will complete baseline measures, including demographics, smoking beliefs and behaviours and provide necessary details about the pregnancy/antenatal care. The baseline questionnaire will be completed verbally, either face to face or during a telephone/video call. Samples: Saliva and breath samples will be collected, either at the clinic appointment or by the participant. If sample collection in the clinic is not possible, we will post saliva sample kits and individual-use carbon monoxide (iCO) monitors, with instructions, may be sent to participants by post. Women will be asked to send the saliva sample via post in a pre-paid envelope. iCO monitor will be used with a mobile app, which will send the results to the central research team electronically. Saliva sample will only be collected from women recruited in clinic, and randomised to intervention group. Randomisation: Participants will be allocated into one of the two groups by chance, by the Investigator or delegate, using a randomisation website. Referral for stop smoking support: Once randomised, women in the UC group will be referred for standard stop smoking support available in their area at the end of their baseline appointment, as per standard care. Women in the intervention group will receive enhanced preloading telephone support (see below) and will be referred for UC smoking cessation support at the end of the preloading component of the intervention (at quit date, up to 4 weeks post-randomisation). 3. Post-randomisation study pack via post: All women will receive a study starter pack via post. For all women, this will contain: - a "What happens next" information sheet - a standard care information leaflet - if applicable, saliva sample kit(s) with instructions - if applicable, iCO monitor with instructions The intervention group will also receive - 1 week worth of NRT patches (15 mg/16 h), with instructions - a preloading information leaflet - an access to the study website, which will reiterate the information contained in the preloading booklet These resources will complement the advice provided during enhanced preloading telephone support. 4. Intervention (intervention group only) Preloading phase and NRT provision and advice on using NRT in brief lapses: - shortly after dispatch of the starter pack, central research team members will contact participants in the intervention group. They will receive up to 4 weekly telephone/video support calls delivered by a university researcher. The number of calls will depend on when the quit date is set up (e.g. if the quit date is set up in 1 week, participants will only receive the first call, at the end of which they will be referred for standard smoking cessation support). Call 1 - The researcher will explain how to use the NRT received in the starter pack for preloading. The use of NRT in brief smoking lapsed will also be discussed. The researcher will help women set a quit date, at least 1 week but no more than 4 weeks ahead. Calls 2-3 - The researcher will ask women how they got on with the NRT; reinforce preloading/brief lapse advice; more NRT will be issued if needed. Final call - During the final call before the quit date, the researcher will refer women for standard smoking cessation support in their area, as described above. Data collection - Preloading phase (Pilot only): During the first 9 months of the trial (in-trial pilot) saliva and/or CO sample will be collected from a sub-sample of women who use NRT for preloading. 5. Standard smoking cessation support which combines behavioural support and provision of NRT, will be offered to all participants (UC group - at baseline; intervention group - after preloading phase). Smoking cessation support varies in different areas. If no specialist services are available in an area, the researchers will refer women for cessation support to their GP/midwife. 6. Data collection - follow up (FU) 1 (6 weeks post-randomisation): An online questionnaire (approx. 10 minutes) including smoking behaviours since randomisation, NRT use and access to stop smoking services. If unable to collect data via an online questionnaire, the research team will attempt to obtain data via telephone, text message or post. 7. Intervention (intervention group only) Reduction phase - advice and NRT provision: Women who report smoking at FU1 will be contacted by the central team researcher via telephone and offered a re-referral for smoking cessation support. Those who refuse will be offered the reduction phase of the intervention. If they accept this, they will receive 2 weeks supply of NRT via post. The researcher will advise them to use NRT (patches and/or inhalators) daily and smoke less than usual. NRT will be repeated on demand unless the participant reports smoking more than at baseline or more than 10 cigarettes each day, for 2 consecutive weeks. They will also receive bi-weekly telephone/video call support and supportive text messages, until up to 36 weeks gestation. NicUse App - throughout the reduction phase, women will be instructed to report smoking and NRT/e-cigarette use via a smartphone application, daily. They will receive instructions, a link to the app and login details. This is for self-monitoring purposes. 8. Data collection - FU2, at 36 weeks gestation or at childbirth, whichever is soonest. An online questionnaire (approx. 10 minutes), including smoking behaviours, stop smoking support. If unable to collect data via an online questionnaire, the central research team will attempt to obtain data via telephone, text message or post. Data may be obtained by site trial staff during antenatal appointments. Validation of smoking status - women who report long term quit (between FU1 and FU2) or at least 50% smoking reduction, will be asked to provide saliva and/or breath sample (using methods as described at baseline) to confirm smoking status. 9. Maternal and birth outcomes - after birth (up to 10 weeks postpartum) we will request these data from the hospital or GP. 10. Interviews to improve recruitment (Pilot only): Potentially eligible women who provide contact details via screening questionnaire, both those who agree to participate in the trial and those who decline, will be invited to take part in a telephone interview, lasting approx. 40 minutes. They will be asked to discuss the factors that influenced their decision to join or not. Interviews will be audio recorded. Incentives: Women will be offered £5 shopping vouchers for completing each FU questionnaire. They will be offered a £20 voucher for saliva/CO samples (except baseline) and a £20 voucher for taking part in the interview. _____ Original interventions: The study design is randomised control trial (RCT) recruiting from antenatal settings and via online recruitment. There will be two trial arms. The control arm will receive standard stop smoking cessation care available for pregnant women, which may include the provision of nicotine replacement therapy (NRT) during the quit attempt (UC group). The intervention arm participants, in addition to standard care, will receive behavioural support and NRT for preloading (using NRT to gradually reduce smoking, until they quit on their agreed quit date) and advice on using NRT in brief smoking lapses during the quit attempt. Women who are unable to quit 6 weeks post-randomisation will receive NRT and advice on using it to reduce smoking. The researchers will compare the following between the intervention and the UC group: 1. Long-term abstinence from smoking reported between six weeks after randomisation and 36 weeks gestation or childbirth, whichever is earlier, confirmed by saliva and/or breath sample; 2. Reported 7-day smoking abstinence at 6 weeks after randomisation 3. Reported and validated 7-day smoking abstinence at 36 weeks gestation (or childbirth, if sooner) 4. Reported and validated ≥50% reduction in daily cigarettes at 36 weeks gestation 5. Exhaled CO concentration at delivery 6. Adverse pregnancy outcome rates(e.g. low birth weight for gestational age, premature birth) The researchers will recruit 1430 pregnant women who are ≤25 weeks gestation, smoke, are willing to use NRT and wish to receive support to stop smoking. They will ask the woman's GP to confirm there are no contraindications to NRT use. The researchers anticipate the recruitment will take 30 months. Participants will be recruited from approximately 12 weeks gestation. They will collect follow up data from participants at 6 weeks post-randomisation and at around 36 weeks gestation. They will collect birth and maternal outcome data from the hospital after birth, and no later than 10 weeks postpartum. Therefore, the maximum duration of the study for any participant would be approximately 38 weeks. Staff involved in the trial procedures will include: 1. Site trial staff: Clinical Research Network (CRN) staff, research nurses, research midwives or any local site staff delegated by the site PI 2. Central research team: smoking in pregnancy (SIP) researchers, SIP administrators or any staff delegated by the CI 1. Participant identification and screening: A screening questionnaire (paper or electronic) will be used in all settings to identify potentially eligible women. A paper or electronic copy of the patient information sheet (PIS) will be made available to women at this point. Those potentially eligible and interested will be asked to provide their contact details and will have the opportunity to discuss the study with a researcher. Participants will be identified in the following settings: 1. Antenatal hospital recruitment settings - face to face by the usual clinical care team. The care team may pre-identify potential participants and send them a letter or email with a screening questionnaire, PIS and consent form before their appointment. Alternatively, the care team or local site trial staff may approach women during appointments, introduce the study/offer PIS and ask women to complete the screening questionnaire. Posters will also be put in relevant clinical areas and women will be able to access the screening questionnaire and PIS via a link or by scanning a code on the poster. 2. Participant Identification Centres (PICs) in antenatal hospital settings - the usual care team or site trial staff will identify potential participants as above and will pass their details to the central research team. 3. Community midwives may also refer potentially eligible and interested women to the central research team, using the screening questionnaire. 4. Online adverts targeted towards pregnant women who smoke - women will be directed to a link to the PIS and screening questionnaire. Their details will be passed on to the central research team. Central research team staff will contact women identified in PICs, by community midwives and online, to discuss the study in more detail. (Note - currently the researchers have not identified any PIC sites, but we may include sites that wish to act as PICs in the future). Recruitment: 1. Participants identified in hospital recruitment settings will discuss the study with site trial staff who will talk them through the PIS and answer any questions. Women who had the chance to fully understand the study and are happy to give their consent will be recruited during the appointment. Women who would like more time to decide will be contacted at least 24 hours later to further discuss their participation. The site trial staff will collect consent, either face to face or by telephone. 2. Participants identified in PICs, by community midwives and online will be contacted via telephone/video call by a central research team member, who will discuss the study with them. For those who do not recall receiving a PIS, a copy will be sent electronically at least 24 hours before consent. 2. Baseline appointment: Consent: Informed consent will be collected from all participants before any intervention or data collection. An Investigator or their delegate will go through the consent form with the potential participant, answer questions and obtain consent. Consent will be collected either face to face or using 'distanced' consent via telephone or video call. Women will be asked to tick or initial each consent item and sign the consent form, either using paper (face to face only) or electronic form (e-consent; face to face or distanced). When obtaining distanced consent, if e-consent is not possible (e.g. if there is no internet connection) verbal telephone consent will be obtained, following a strict scripted protocol, which will follow the same consent items as the 'hard copy' consent form. Eligibility will be formally confirmed once consent is collected. Very brief advice (VBA) for smoking cessation in pregnancy: As part of the baseline appointment, all women will receive VBA as defined by the National Centre for Smoking Cessation Training (NCSCT). This is part of standard care for smoking cessation in pregnancy. VBA comprises (1) carbon monoxide (CO) testing, (2) advice that intensive behavioural support enhances success with quitting and (3) referral for this, if available locally. Data collection at baseline: Participants will complete baseline measures, including demographics, smoking beliefs and behaviours and provide necessary details about the pregnancy/antenatal care. The baseline questionnaire will be completed verbally, either face to face or during a telephone/video call. Samples: Saliva and breath samples will be collected, either at the clinic appointment or by the participant. If sample collection in the clinic is not possible, we will post saliva sample kits and individual-use carbon monoxide (iCO) monitors, with instructions, by post. Women will be asked to send the saliva sample via post in a pre-paid envelope. iCO monitor will be used with a mobile app, which will send the results to the central research team electronically. Randomisation: Participants will be allocated into one of the two groups by chance, by the Investigator or delegate, using a randomisation website. Referral for stop smoking support: Once randomised, women in the UC group will be referred for standard stop smoking support available in their area at the end of their baseline appointment, as per standard care. Women in the intervention group will receive enhanced preloading telephone support (see below) and will be referred for UC smoking cessation support at the end of the preloading component of the intervention (at quit date, up to 4 weeks post-randomisation). 3. Post-randomisation study pack via post: All women will receive a study starter pack via post. For all women, this will contain: - a "What happens next" information sheet - a standard care information leaflet - if applicable, saliva sample kit(s) with instructions - if applicable, iCO monitor with instructions The intervention group will also receive - 1 week worth of NRT patches (15 mg/16 h), with instructions - a preloading information leaflet - an access to the study website, which will reiterate the information contained in the preloading booklet These resources will complement the advice provided during enhanced preloading telephone support. 4. Intervention (intervention group only) Preloading phase and NRT provision and advice on using NRT in brief lapses: - shortly after dispatch of the starter pack, central research team members will contact participants in the intervention group. They will receive up to 4 weekly telephone/video support calls delivered by a university researcher. The number of calls will depend on when the quit date is set up (e.g. if the quit date is set up in 1 week, participants will only receive the first call, at the end of which they will be referred for standard smoking cessation support). Call 1 - The researcher will explain how to use the NRT received in the starter pack for preloading. The use of NRT in brief smoking lapsed will also be discussed. The researcher will help women set a quit date, at least 1 week but no more than 4 weeks ahead. Calls 2-3 - The researcher will ask women how they got on with the NRT; reinforce preloading/brief lapse advice; more NRT will be issued if needed. Final call - During the final call before the quit date, the researcher will refer women for standard smoking cessation support in their area, as described above. Data collection - Preloading phase (Pilot only): During the first 9 months of the trial (in-trial pilot) saliva and/or CO sample will be collected from a sub-sample of women who use NRT for preloading. 5. Standard smoking cessation support which combines behavioural support and provision of NRT, will be offered to all participants (UC group - at baseline; intervention group - after preloading phase). Smoking cessation support varies in different areas. If no specialist services are available in an area, the researchers will refer women for cessation support to their GP/midwife. 6. Data collection - follow up (FU) 1 (6 weeks post-randomisation): An online questionnaire (approx. 10 minutes) including smoking behaviours since randomisation, NRT use and access to stop smoking services. If unable to collect data via an online questionnaire, the research team will attempt to obtain data via telephone, text message or post. 7. Intervention (intervention group only) Reduction phase - advice and NRT provision: Women who report smoking at FU1 will be contacted by the central team researcher via telephone and offered a re-referral for smoking cessation support. Those who refuse will be offered the reduction phase of the intervention. If they accept this, they will receive 2 weeks supply of NRT via post. The researcher will advise them to use NRT (patches and/or inhalators) daily and smoke less than usual. NRT will be repeated on demand unless the participant reports smoking more than at baseline or more than 10 cigarettes each day, for 2 consecutive weeks. They will also receive bi-weekly telephone/video call support and supportive text messages, until up to 36 weeks gestation. NicUse App - throughout the reduction phase, women will be instructed to report smoking and NRT/e-cigarette use via a smartphone application, daily. They will receive instructions, a link to the app and login details. This is for self-monitoring purposes. 8. Data collection - FU2, at 36 weeks gestation or at childbirth, whichever is soonest. An online questionnaire (approx. 10 minutes), including smoking behaviours, stop smoking support. If unable to collect data via an online questionnaire, the central research team will attempt to obtain data via telephone, text message or post. Data may be obtained by site trial staff during antenatal appointments. Validation of smoking status - women who report long term quit (between FU1 and FU2) or at least 50% smoking reduction, will be asked to provide saliva and/or breath sample (using methods as described at baseline) to confirm smoking status. 9. Maternal and birth outcomes - after birth (up to 10 weeks postpartum) we will request these data from the hospital or GP. 10. Interviews to improve recruitment (Pilot only): Potentially eligible women who provide contact details via screening questionnaire, both those who agree to participate in the trial and those who decline, will be invited to take part in a telephone interview, lasting approx. 40 minutes. They will be asked to discuss the factors that influenced their decision to join or not. Interviews will be audio recorded. Incentives: Women will be offered £5 shopping vouchers for completing each FU questionnaire. They will be offered a £20 voucher for saliva/CO samples (except baseline) and a £20 voucher for taking part in the interview. |
| Intervention type | Mixed |
| Primary outcome measure | Biochemically validated, prolonged abstinence from smoking self-reported between 6 weeks after randomisation and 36 weeks gestation or childbirth, whichever is earlier. Biochemical validation: cotinine/anabasine levels in saliva sample and/or CO levels tested using CO monitor. Timepoint: 36 weeks gestation or at childbirth, whichever is the soonest. |
| Secondary outcome measures | Current secondary outcome measures as of 21/11/2023: Smoking-related: 1. Reported and validated 7-day smoking abstinence at 36 weeks gestation (measured by self-reported follow-up questionnaire, saliva sample analysed for cotinine and/or anabasine, exhaled breath sample for carbon monoxide levels) 2. Self-reported ≥50% reduction in daily cigarettes at 36 weeks gestation 3. Exhaled CO concentration at delivery (measured by exhaled breath sample for carbon monoxide levels) 4. Whether or not brief smoking lapse experienced, reported at 6 weeks post randomisation (self report) Pregnancy and safety-related (collected from medical records at birth or up to 10 weeks postpartum): 1. Miscarriage (patient notes) 2. Stillbirth (patient notes) 3. Low birth weight for gestational age (patient notes) 4. Unadjusted birthweight and birthweight z score (patient notes) 5. Premature birth (patient notes) 6. Gestation at birth (patient notes) 7. Congenital abnormality (patient notes) 8. Mode of delivery (patient notes) 9. Admission to special care (patient notes) 10. Neonatal death (patient notes) Exploratory outcomes: 1. Cigarettes per day when using NRT for ‘preloading’ or to cut down smoking (self report) 2. Exhaled CO when using NRT for ‘preloading’ or to cut down smoking (measured by exhaled breath sample for carbon monoxide levels) at around day 7 3. Saliva cotinine concentration when using NRT for ‘preloading’ or to cut down smoking (saliva sample analysed for cotinine and/or anabasine) at around day 7 4. Use of stop smoking support (self report) measured using self-report – follow up 1 questionnaire at 6 weeks after randomisation Previous secondary outcome measures: Smoking-related: 1. Reported 7-day smoking abstinence at 6 weeks after randomisation 2. Reported and validated 7-day smoking abstinence at 36 weeks gestation (cotinine/anabasine levels in saliva sample and/or CO levels tested using CO monitor) 3. Reported and validated ≥50% reduction in daily cigarettes at 36 weeks gestation 4. Exhaled CO concentration measured using CO monitor at delivery 5. Whether or not brief smoking lapse experienced, reported at 6 weeks after randomisation NB: If delivery occurs before 36 weeks gestation, outcomes intended for collection at 36 weeks will be collected then Pregnancy and safety-related (collected from medical records at birth or up to 10 weeks postpartum): 1. Miscarriage 2. Stillbirth 3. Low birth weight for gestational age 4. Unadjusted birthweight and birthweight z score 5. Premature birth 6. Gestation at birth 7. Congenital abnormality 8. Mode of delivery 9. Admission to special care 10. Neonatal death Exploratory outcomes: 1. Exhaled CO when using NRT for ‘preloading’ or to cut down smoking measured using CO monitor at around day 7 2. Saliva cotinine concentration when using NRT for ‘preloading’ or to cut down smoking measured using saliva sample at around day 7 3. Use of stop smoking support measured using self-report – follow up 1 questionnaire at 6 weeks after randomisation 4. Reported use of NRT before the quit date and in brief smoking lapses measured using self-report – FU1 questionnaire |
| Overall study start date | 05/04/2019 |
| Overall study end date | 31/10/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Female |
| Target number of participants | Planned Sample Size: 1430; UK Sample Size: 1430 |
| Participant inclusion criteria | Current inclusion criteria as of 08/03/2022: Women of any age who: 1. Are <25 weeks’ gestation and have been referred for or have received or attended an intment as part of standard antenatal care 2. Smoke ≥ 5 daily cigarettes 3. Willing to set a quit date and accept referral to SSS 4. Willing to use NRT patch to try to stop smoking 5. Able to understand written and spoken English 6. Able to give consent _____ Previous inclusion criteria: Women of any age who: 1. Are ≤25 weeks’ gestation with dating ultrasound-confirmed pregnancies 2. Smoke ≥5 daily cigarettes 3. Willing to set a quit date and accept referral to SSS 4. Are willing to use an NRT patch to try to stop smoking 5. Able to give consent |
| Participant exclusion criteria | Current exclusion criteria as of 21/11/2023: 1. Already in a cessation study 2. Contraindications to NRT including: known severe reaction/hypersensitivity to NRT, recent cardiovascular/cerebrovascular event or changes and taking theophylline/clozapine 3. Currently uses e-cigarette every day or more frequently Previous exclusion criteria: 1. Already in a cessation study 2. Currently uses e-cigarettes daily or more frequently 3. Contraindications to NRT including: severe cardiovascular disease, unstable angina, cardiac arrhythmias, recent cerebrovascular accident or transient ischaemic attack (TIA), chronic, generalized skin disorders or sensitivity to nicotine patches, chemical dependence/alcohol addiction or major fetal anomalies 4. Not able to read or understand text written in English |
| Recruitment start date | 01/04/2022 |
| Recruitment end date | 31/12/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
Royal Berkshire Hospital
London Road
Reading
RG1 5AN
United Kingdom
Reading
RG1 5AN
United Kingdom
New Cross Hospital
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Warrington Hospital
Lovely Lane
Warrington
WA5 1QG
United Kingdom
Warrington
WA5 1QG
United Kingdom
Milton Keynes University Hospital
Standing Way
Eaglestone
Milton Keynes
MK6 5LD
United Kingdom
Eaglestone
Milton Keynes
MK6 5LD
United Kingdom
Worcestershire Royal Hospital
Charles Hastings Way
Worcester
WR5 1DD
United Kingdom
Worcester
WR5 1DD
United Kingdom
Birmingham Children's Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom
Birmingham
B4 6NH
United Kingdom
Leighton Hospital
Leighton
Crewe
CW1 4QJ
United Kingdom
Crewe
CW1 4QJ
United Kingdom
University Hospital of Hartlepool
Holdforth Road
Hartlepool
TS24 9AH
United Kingdom
Hartlepool
TS24 9AH
United Kingdom
University of Nottingham
School of Medicine and Health Sciences
University Park
Nottingham
NG7 2RD
United Kingdom
University Park
Nottingham
NG7 2RD
United Kingdom
The Royal London Hospital
80 Newark Street
London
E1 2ES
United Kingdom
London
E1 2ES
United Kingdom
The Hillingdon Hospitals NHS Foundation Trust
Pield Heath Road
Uxbridge
UB8 3NN
United Kingdom
Uxbridge
UB8 3NN
United Kingdom
North Cumbria Integrated Care NHS Foundation Trust
Pillars Building
Cumberland Infirmary
Infirmary Street
Carlisle
CA2 7HY
United Kingdom
Cumberland Infirmary
Infirmary Street
Carlisle
CA2 7HY
United Kingdom
Wirral University Teaching Hospital NHS Foundation Trust
Arrowe Park Hospital
Arrowe Park Road
Upton
Wirral
CH49 5PE
United Kingdom
Arrowe Park Road
Upton
Wirral
CH49 5PE
United Kingdom
Walsall Healthcare NHS Trust
Manor Hospital
Moat Road
Walsall
WS2 9PS
United Kingdom
Moat Road
Walsall
WS2 9PS
United Kingdom
The Princess Alexandra Hospital
Hamstel Road
Harlow
CM20 1QX
United Kingdom
Harlow
CM20 1QX
United Kingdom
Manchester University NHS Foundation Trust
St Marys Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Sandwell and West Birmingham Hospitals NHS Trust
City Hospital
Dudley Road
Birmingham
B18 7QH
United Kingdom
Dudley Road
Birmingham
B18 7QH
United Kingdom
University Hospitals Dorset NHS Foundation Trust
Management Offices
Poole Hospital
Longfleet Road
Poole
BH15 2JB
United Kingdom
Poole Hospital
Longfleet Road
Poole
BH15 2JB
United Kingdom
Royal Free London NHS Foundation Trust
Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Sherwood Forest Hospitals NHS Foundation Trust
Kings Mill Hospital
Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom
Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom
Buckinghamshire Healthcare NHS Trust
Amersham Hospital
Whielden Street
Amersham
HP7 0JD
United Kingdom
Whielden Street
Amersham
HP7 0JD
United Kingdom
Stoke Mandeville Hospital
Mandeville Road
Aylesbury
HP21 8AL
United Kingdom
Aylesbury
HP21 8AL
United Kingdom
Royal Cornwall Hospitals NHS Trust
Royal Cornwall Hospital
Treliske
Truro
TR1 3LJ
United Kingdom
Treliske
Truro
TR1 3LJ
United Kingdom
Great Western Hospitals NHS Foundation Trust
Great Western Hospital
Marlborough Road
Swindon
SN3 6BB
United Kingdom
Marlborough Road
Swindon
SN3 6BB
United Kingdom
Cwm Taf NHS Trust
Dewi Sant Hospital
Albert Road
Pontypridd
CF37 1LB
United Kingdom
Albert Road
Pontypridd
CF37 1LB
United Kingdom
Bolton NHS Foundation Trust
The Royal Bolton Hospital
Minerva Road
Farnworth
Bolton
BL4 0JR
United Kingdom
Minerva Road
Farnworth
Bolton
BL4 0JR
United Kingdom
Powys Teaching Lhb
Bronllys Hospital
Bronllys
Brecon
LD3 0LS
United Kingdom
Bronllys
Brecon
LD3 0LS
United Kingdom
London North West University Healthcare NHS Trust
Northwick Park Hospital
Watford Road
Harrow
HA1 3UJ
United Kingdom
Watford Road
Harrow
HA1 3UJ
United Kingdom
Swansea Lhb
Kidwelly House, Charter Court
Phoenix Way
Swansea Enterprise Park
Swansea
SA7 9FS
United Kingdom
Phoenix Way
Swansea Enterprise Park
Swansea
SA7 9FS
United Kingdom
Epsom and St Helier University Hospitals NHS Trust
St Helier Hospital
Wrythe Lane
Carshalton
SM5 1AA
United Kingdom
Wrythe Lane
Carshalton
SM5 1AA
United Kingdom
East Lancashire Hospitals NHS Trust
Royal Blackburn Hospital
Haslingden Road
Blackburn
BB2 3HH
United Kingdom
Haslingden Road
Blackburn
BB2 3HH
United Kingdom
Cardiff & Vale University Lhb
Woodland House
Maes-y-coed Road
Cardiff
CF14 4HH
United Kingdom
Maes-y-coed Road
Cardiff
CF14 4HH
United Kingdom
Aneurin Bevan Lhb - Caerphilly Locality Office
Llanarth House
Newbridge Gateway
Bridge Street
Newport
NP11 5GH
United Kingdom
Newbridge Gateway
Bridge Street
Newport
NP11 5GH
United Kingdom
County Durham and Darlington NHS Foundation Trust
Darlington Memorial Hospital
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom
Hull University Teaching Hospitals NHS Trust
Bay 2 - Specialist Midwives Office
Antenatal Day Unit
Women’s & Children’s Hospital
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Antenatal Day Unit
Women’s & Children’s Hospital
Anlaby Road
Hull
HU3 2JZ
United Kingdom
York and Scarborough Teaching Hospitals
Surgery and Family Health
LARC
York Hospital
Wigginton Road
York
YO31 8HE
United Kingdom
LARC
York Hospital
Wigginton Road
York
YO31 8HE
United Kingdom
Sponsor information
University of Nottingham
University/education
University/education
Research and Innovation
East Atrium
Jubilee Conference centre
Triumph Road
Nottingham
NG8 1DH
England
United Kingdom
| Phone | +44 (0)11584667906 |
|---|---|
| sponsor@nottingham.ac.uk | |
| Website | http://www.nottingham.ac.uk/ |
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Government
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR129210
No information available
Results and Publications
| Intention to publish date | 31/01/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. The protocol and statistical analysis plan will be available at a later date. |
| IPD sharing plan | The current data-sharing plans for this study are unknown and will be available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Interview version 1.0 |
25/08/2021 | 13/10/2021 | No | Yes |
| Participant information sheet | Pilot version 1.0 |
25/08/2021 | 13/10/2021 | No | Yes |
| Participant information sheet | Trial version 1.0 |
25/08/2021 | 13/10/2021 | No | Yes |
| HRA research summary | 26/07/2023 | No | No |
Additional files
Editorial Notes
14/11/2024: Hull University Teaching Hospitals NHS Trust and York and Scarborough Teaching Hospitals were added to the study participating centres.
11/11/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 01/11/2024 to 31/12/2025.
2. The intention to publish date was changed from 25/05/2026 to 31/01/2027.
22/05/2024: The following changes were made to the study record:
1. The overall study end date was changed from 25/05/2025 to 31/10/2026.
2. Epsom and St Helier University Hospitals NHS Trust, East Lancashire Hospitals NHS Trust, Cardiff & Vale University Lhb, Aneurin Bevan Lhb - Caerphilly Locality Office, County Durham and Darlington NHS Foundation Trust were added to the study participating centres.
21/11/2023: The following changes were made to the study record:
1. The interventions, secondary outcome measures and exclusion criteria were updated.
2. The recruitment end date was changed from 01/10/2024 to 01/11/2024.
3. Wales was added to the countries of recruitment.
4. The study participating centres were updated to remove Countess of Chester Hospital, John Radcliffe Hospital, Whiston Hospital, Amersham Hospital, Queen Elizabeth Hospital, Freeman Hospital, Sunderland Royal Hospital, Birmingham City Hospital, Royal Devon & Exeter Hospital, Yeovil District Hospital NHS Foundation Trust, Salisbury District Hospital, and Blackpool Teaching Hospitals NHS Foundation Trust; and to add The Princess Alexandra Hospital, Manchester University NHS Foundation Trust, Sandwell and West Birmingham Hospitals NHS Trust, University Hospitals Dorset NHS Foundation Trust, Royal Free London NHS Foundation Trust, Sherwood Forest Hospitals NHS Foundation Trust, Buckinghamshire Healthcare NHS Trust, Stoke Mandeville Hospital, Royal Cornwall Hospitals NHS Trust, Great Western Hospitals NHS Foundation Trust, Cwm Taf NHS Trust, Bolton NHS Foundation Trust, Powys Teaching Lhb, London North West University Healthcare NHS Trust - Northwick Park Hospital, and Swansea Lhb.
08/03/2022: The following changes were made to the trial record:
1. The interventions were changed.
2. The inclusion criteria were changed.
3. The recruitment start date was changed from 01/03/2022 to 01/04/2022.
4. The recruitment end date was changed from 01/09/2024 to 01/10/2024.
5. The trial participating centres James Cook University Hospital, Royal Shrewsbury Hospital, Royal Stoke University Hospital were removed.
6. The trial participating centres Yeovil District Hospital, The Hillingdon Hospitals NHS Foundation Trust, Salisbury District Hospital, North Cumbria Integrated Care NHS Foundation Trust, Blackpool Teaching Hospitals NHS Foundation Trust, Wirral University Teaching Hospital NHS Foundation Trust, Walsall Healthcare NHS Trust were added.
13/10/2021: Trial's existence confirmed by the NIHR.
