Plain English Summary
Background and study aims
Smoking in pregnancy remains an unresolved issue. Quit rates in pregnant smokers are low and advice by doctors and nurses, even when combined with behavioural support and nicotine replacement treatment (NRT), has only a limited effect. NRT (e.g. nicotine patch) has shown little effect most likely because pregnant women use them very little. Pregnant women also use up nicotine faster, and standard NRT doses may be too slow and too low for them. Nicotine patches also do not allow the dose to be tailored to smokers’ needs. Electronic cigarettes (EC) may overcome these limitations. ECs allow flexible dosing and have a faster effect than NRT. They also provide some of the sensations and enjoyment that smokers get from smoking. These characteristics should ensure better treatment uptake. It is estimated that in the UK half a million smokers have switched from smoking to vaping (EC use) so far, with some 20,000 quitting smoking with the help of EC per year who would not have quit otherwise. The EC must therefore be tested as a stop-smoking treatment for pregnant women, but the safety of such treatment needs to be addressed. ECs do not contain most of the chemicals responsible for health risks of smoking and those that are present are there at levels much lower than those present in cigarette smoke. The overall risks of EC use are estimated to be 95% less than risks of smoking. No chemicals other than nicotine have been identified in EC vapour that would be expected to affect the health of the baby. NRT is universally used by the UK pregnancy stop smoking services because pregnant smokers are consuming nicotine anyway and because the harm to the baby is also caused by other chemicals in tobacco smoke which are absent in NRT. The same logic applies to nicotine intake from ECs. The safety concerns are reduced by the fact that ECs would be used as a replacement for cigarettes which pose well known dangers. If there is any sign of an increased risk, the study can be stopped. If such use involves risks, evidence of this would have important practical implications. The aim of this study is to find out whether ECs are more effective at helping pregnant women to quit smoking than NRT.
Who can participate?
Women aged 18 or over, who are 12 to 24 weeks pregnant, smoke daily and want help with stopping smoking
What does the study involve?
Participants are randomly allocated to use either an EC or nicotine patches. The products are posted out to participants, and they are called by a stop smoking advisor shortly after to check they know how to use the product and to set a quit day. The advisor then calls the participant weekly for a further 5 weeks to provide support and check on their progress. Participants are followed up at the end of their pregnancy and also at 3 months after birth. Smoking quit rates and side effects from the two treatments are compared at end of pregnancy and at 3 months after birth.
What are the possible benefits and risks of participating?
The benefit to participants is that taking part may help them to stop smoking, improving not only their health, but also the health and wellbeing of their baby. A positive result would also provide a new, inexpensive, and practical way to tackle an important and so far unresolved problem. No risks to participants are expected. Nicotine patches are approved to be used in pregnancy, and ECs do not pose any risks greater than cigarettes, which participants are already smoking.
Where is the study run from?
Queen Mary University of London (UK)
When is the study starting and how long is it expected to run for?
May 2017 to November 2020 (updated 14/04/2021, previously: April 2021)
Who is funding the study?
NIHR Health Technology Assessment Programme (UK)
Who is the main contact?
Dr Dunja Przulj
Study website
Additional identifiers
EudraCT/CTIS number
2017-001237-65
IRAS number
ClinicalTrials.gov number
Nil known
Secondary identifying numbers
011822; HTA 15/57/85
Study information
Scientific title
Helping pregnant smokers quit: a multi-centre RCT of electronic cigarette and nicotine patches
Acronym
PREP
Study hypothesis
Smoking in pregnancy remains an unresolved issue. Quit rates in pregnant smokers are low and advice by doctors and nurses, even when combined with behavioural support and nicotine replacement treatment (NRT) has only limited efficacy. NRT has shown little effect most likely because pregnant women use them very little. Pregnant women also metabolise nicotine faster and standard NRT doses may be too slow and too low for them. Nicotine patches also do not allow dosing tailored to smokers’ needs.
Electronic cigarettes (EC) may overcome these limitations. EC allow flexible dosing and have a faster effect than NRT. They also provide some of the sensations and enjoyment that smokers get from smoking. These characteristics should ensure better treatment adherence.
The trialists hypothesise that EC may be more effective in helping pregnant women to quit smoking than NRT.
More details can be found at: https://www.journalslibrary.nihr.ac.uk/programmes/hta/155785/#/
Ethics approval(s)
London- South East Research Ethics Committee, 29/06/2017, REC ref: 17/LO/0962
Study design
Multi-centre open-label randomized controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Smoking cessation
Intervention
Randomisation will be conducted by a web-based application system created by the trialists' clinical trials unit. Randomisation will be in blocks of mixed sizes. Allocation is 1:1.
Participants will be randomised (1:1) to receive either nicotine patches for up to 8 weeks (15mg/16hr) or an e-cigarette starter pack. Both groups will receive weekly telephone support for 6 weeks from specialist stop smoking advisors. Participants will be follow up at the end of pregnancy and at 3 months postpartum.
Intervention type
Mixed
Primary outcome measure
Prolonged abstinence rates at the end of pregnancy, defined as per Russell Standard (up to 5 lapses allowed from 2 weeks after the target quit day until end of pregnancy, with no smoking at all during the previous week at the time of follow-up), and verified by salivary cotinine (< 15 ng/ml) for those not reporting using any nicotine product and anabasine (< 1 ng/ml) for those reporting other forms of nicotine use.
Secondary outcome measures
1. Smoke intake and nicotine intake, measured by salivary anabasine and salivary cotinine levels, assessed for participants still using NRT or EC at end of pregnancy and for ‘dual users’
2. 7-day point-prevalence abstinence (not a puff in the last 7 days), self-reported at 4 weeks, end of pregnancy and at 3 months post-partum
3. Prolonged abstinence, self-reported at end of pregnancy and 3 months post-partum
4. Use of NRT and EC throughout pregnancy, measured by asking participants on how many days they used their products at each weekly contact and at follow-ups
5. Safety examined by looking at the proportion of participants reporting adverse events and serious adverse events in each group throughout pregnancy; proportion of participants in each group reporting adverse events and serious adverse events for themselves or their infant at 3 months post-partum; and differences in birth and maternal outcomes between the two groups
Overall study start date
01/05/2017
Overall study end date
26/11/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Daily smokers
2. 12 to 24 weeks pregnant
3. Wants help with stopping smoking
4. Willing to be randomised to use either NRT or EC (to avoid selective drop-out and contamination)
5. Wiling to receive 6 weekly support calls over the phone plus two follow-up calls
6. Speaks English (to allow data collection via phone)
7. Aged 18 years or over
Participant type(s)
Healthy volunteer
Age group
Adult
Lower age limit
18 Years
Sex
Female
Target number of participants
1,142
Total final enrolment
1140
Participant exclusion criteria
1. Known allergic reaction to nicotine skin patches (a contraindication for patch use)
2. Current daily use of NRT or EC
3. Taking part in another interventional trial
4. Serious medical problem or high-risk pregnancy (to avoid problems with follow-up and data collection)
Recruitment start date
01/01/2018
Recruitment end date
07/11/2019
Locations
Countries of recruitment
England, Scotland, United Kingdom
Study participating centre
Queen Mary University of London
E1 4AH
United Kingdom
Study participating centre
Countess of Chester Hospital
Chester
CH2 1UL
United Kingdom
Study participating centre
Royal Preston Hospital
Preston
PR2 9HT
United Kingdom
Study participating centre
Leighton Hospital
Crewe
CW1 4QJ
United Kingdom
Study participating centre
Warrington & Halton Hospital
Warrington
WA5 1QG
United Kingdom
Study participating centre
Queen Elizabeth Hospital Gateshead
Gateshead
NE9 6SX
United Kingdom
Study participating centre
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom
Study participating centre
Sunderland Royal Hospital
Sunderland
SR4 7TP
United Kingdom
Study participating centre
Cumberland Infirmary
Carlisle
CA2 7HY
United Kingdom
Study participating centre
Bradford Royal Hospital
Bradford
BD9 6RJ
United Kingdom
Study participating centre
St Mary's Hospital, Manchester
Manchester
M13 9WL
United Kingdom
Study participating centre
Burnley General
Burnley
BB10 2PQ
United Kingdom
Study participating centre
North Manchester General/ Royal Oldham
Manchester
M8 5RB
United Kingdom
Study participating centre
Birmingham Womens Hospital
Birmingham
B15 2TG
United Kingdom
Study participating centre
Royal Stoke Hospital
Stoke-on-Trent
ST4 6QG
United Kingdom
Study participating centre
Birmingham City Hospital
Birmingham
B18 7QH
United Kingdom
Study participating centre
Princess Royal Hospital, Telford
Telford
TF1 6TF
United Kingdom
Study participating centre
Royal Devon & Exeter Hospital
Exeter
EX2 5DW
United Kingdom
Study participating centre
Derriford Hospital, Plymouth
Plymouth
PL6 8DH
United Kingdom
Study participating centre
NHS Forth Valley
Stirling
FK9 4SW
United Kingdom
Study participating centre
Nottingham University Hospitals
Nottingham
NG7 2UH
United Kingdom
Study participating centre
Russels Hall, Dudley
Dudley
DY1 2HQ
United Kingdom
Study participating centre
University Hospitals of Derby & Burton
Derby
DE22 3NE
United Kingdom
Study participating centre
Heart of England NHS
Birmingham
B9 5SS
United Kingdom
Sponsor information
Organisation
Queen Mary University of London
Sponsor details
Joint Research Management Office
QM Innovation Building
5 Walden Street
London
E1 2EF
England
United Kingdom
Sponsor type
University/education
Website
ROR
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The results of the study will be published in a high-impact peer reviewed journal.
Intention to publish date
01/05/2022
Individual participant data (IPD) Intention to share
Yes
IPD sharing plan
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Dunja Przulj.
Added 12/09/2017:
Once the study is published, if a researcher/academic requests the dataset or part of the dataset (for example if conducting a review/meta-analysis), then they will be provided with the Excel data file if necessary. Data is archived electronically for 20 years. Any data shared will be completely anonymised, and as consent has not been requested from participants for this.
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 16/05/2022 | 17/05/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 01/07/2023 | 16/10/2023 | Yes | No |