The carboprost or oxytocin postpartum haemorrhage effectiveness study
| ISRCTN | ISRCTN16416766 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16416766 |
| EudraCT/CTIS number | 2018-001829-11 |
| IRAS number | 235254 |
| Secondary identifying numbers | CPMS 39362, IRAS 235254 |
- Submission date
- 03/09/2018
- Registration date
- 18/10/2018
- Last edited
- 07/04/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
Excessive bleeding after childbirth (postpartum haemorrhage, PPH) is a common and potentially serious problem affecting 1 in 20 women. Each year it causes 75,000 deaths worldwide. It also causes weakness from anaemia, delayed recovery, psychological trauma, and poor breastfeeding and bonding with their baby. Oxytocin is recommended as first line treatment for PPH as it is low cost, effective and has very few side effects. However, the PPH rate is increasing; laboratory studies suggest that repeated use of oxytocin leads to reduced effectiveness. Carboprost is an alternative treatment and there is evidence that it is more effective than oxytocin, but it is usually reserved for second/third line treatment due to side effects of diarrhoea and vomiting and its cost. The aim of this study is to compare the two drugs, carboprost and oxytocin, currently used to treat PPH, to find out whether it is better to use carboprost or oxytocin as the first drug for treatment for PPH.
Who can participate?
Woman aged 16 and over with PPH
What does the study involve?
Participants are randomly allocated to one of two groups. Two injections are administered. One group receives carboprost and placebo (dummy drug) and the other group receives oxytocin and placebo (dummy drug). There are no extra clinic visits required. Data is collected from medical records. Each participant is followed up 24 hours and 4 weeks later to complete a questionnaire and collect information regarding their healthcare resource use and quality of life. Paper follow-up documents are posted to the homes of participants for their completion.
What are the possible benefits and risks of participating?
The results will help doctors know which treatment is better for PPH treatment. The benefits of participation are that women will receive optimal care, with researchers, clinicians and regulators observing and checking their care carefully so as to ensure that no mistakes are made. This is why clinical outcomes of participants in any study tend to be much better than those of non-participants, irrespective of what treatment they receive. The risks are that of the treatments, both of which are already commonly used as part of PPH management. The common side effects of both treatments are as follows: oxytocin: headache, nausea, vomiting, low blood pressure, water retention; carboprost: diarrhoea, vomiting, high temperature, increased blood pressure.
Where is the study run from?
Liverpool Women’s Hospital (UK)
When is the study starting and how long is it expected to run for?
September 2017 to November 2025
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Miss Charlotte Van Netten
cope@liverpool.ac.uk
Contact information
Scientific
Liverpool Clinical Trials Centre, University of Liverpool
2nd Floor, Institute in the Park
Alder Hey Children’s NHS Foundation Trust
Eaton Road
Liverpool
L12 2AP
United Kingdom
| Phone | +44 (0)151 795 8760 |
|---|---|
| cope@liverpool.ac.uk |
Study information
| Study design | Randomized; Both; Design type: Treatment, Drug, Qualitative |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN16416766_PIS_v2.0_26Sep18_Antenatal.pdf |
| Scientific title | Carboprost vs Oxytocin as the First Line Treatment of Primary Postpartum Haemorrhage: A phase IV, double-blind, double-dummy, randomised controlled trial. |
| Study acronym | COPE |
| Study hypothesis | Current study hypothesis as of 07/04/2025: COPE is a research study to compare the two drugs, carboprost and oxytocin, currently used to treat PPH. About 2000 women will take part across approximately 20 UK NHS hospitals, and we want to know if it is better to use carboprost or oxytocin as the first drug for the treatment of PPH. Previous study hypothesis: COPE is a research study to compare the two drugs, carboprost and oxytocin, currently used to treat PPH. About 4000 women will take part across approximately 40 UK NHS hospitals, and we want to know if it is better to use carboprost or oxytocin as the first drug for treatment of PPH. |
| Ethics approval(s) |
Approved 04/10/2018, West Midlands - Coventry & Warwickshire Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, BG1 6FS, United Kingdom; +44 2071048009; coventryandwarwick.rec@hra.nhs.uk), ref: 18/WM/0227 |
| Condition | Postpartum haemorrhage |
| Intervention | Current interventions as of 07/04/2025: COPE aims to recruit 2000 women across 20 UK hospitals via two recruitment pathways: 1. Women at high risk of PPH (defined as relative risk of > 3) will be invited to prospectively consent to participation within COPE and will be approached antenatally by a COPE recruiter who will provide information and the opportunity for discussion. At this point, women will have the opportunity to decline participation in the study, in which case a ""COPE declined"" sticker will be placed in the woman's case notes. 2. Women at low risk of PPH who meet eligibility criteria will be randomised into the trial in the emergency situation, where treatment needs to be given urgently and there is no time for prior consent. Postnatally, full study information will be provided and the woman will be asked to sign the emergency consent form. In the event that capacity is not regained or delayed, a personal or professional legal representative will be approached for informed emergency consent. Participants will be randomised in a 1:1 ratio using random variable block size, stratified by mode of birth (caesarean section or vaginal birth) to one of the following treatment arms: Intervention: Carboprost 250 micrograms by deep intramuscular injection and 1ml placebo by slow intravenous injection. Control: Oxytocin 10 international units by slow intravenous injection and 1ml placebo by deep intramuscular injection. Centres will be provided with a series of sequentially numbered, sealed treatment kits to be received by the pharmacy department and distributed to an appropriate secure location within the delivery suite for ready access upon presentation of eligible patients. A placebo vial will be administered intravenously alongside carboprost and intramuscularly alongside oxytocin in order to conserve the blinding of treatments for both healthcare professionals and participants. This will eradicate any potential bias. The design of this study has been developed to have minimal impact on families, resulting in the need for no extra clinic visits within the trial. Clinical outcome data will be collected from medical records. Each participant will be followed up at 24 hours and 4 weeks post randomisation to obtain data for the childbirth experience questionnaire, and information regarding their resource use and quality of life, where applicable. Such follow-up documents will be paper based and posted to the homes of participating women for their completion. At the time of consent to the main study, participants will also be invited to take part in an embedded study, including; 1. Audio recording of COPE antenatal consent discussions between women and their birth partner (if applicable) and trial recruiters 2. Interviews with women and their birth partners (if applicable) who agree or decline consent including bereaved women; either by telephone or at an agreed location 3. A questionnaire for both women who agree or decline consent to the main trial 4. Focus groups and/or interviews with COPE trial recruiters at each pilot site Previous interventions: COPE aims to recruit 3,948 women across 40 UK hospitals via two recruitment pathways: 1. Women at high risk of PPH (defined as relative risk of > 3) will be invited to prospectively consent to participation within COPE and will be approached antenatally by a COPE recruiter who will provide information and the opportunity for discussion. At this point, women will have the opportunity to decline participation in the study, in which case a ""COPE declined"" sticker will be placed in the woman's case notes. 2. Women at low risk of PPH who meet eligibility criteria will be randomised into the trial in the emergency situation, where treatment needs to be given urgently and there is no time for prior consent. Postnatally, full study information will be provided and the woman will be asked to sign the emergency consent form. In the event that capacity is not regained or delayed, a personal or professional legal representative will be approached for informed emergency consent. Participants will be randomised in a 1:1 ratio using random variable block size, stratified by mode of birth (caesarean section or vaginal birth) to one of the following treatment arms: Intervention: Carboprost 250 micrograms by deep intramuscular injection and 1ml placebo by slow intravenous injection. Control: Oxytocin 10 international units by slow intravenous injection and 1ml placebo by deep intramuscular injection. Centres will be provided with a series of sequentially numbered, sealed treatment kits to be received by the pharmacy department and distributed to an appropriate secure location within the delivery suite for ready access upon presentation of eligible patients. A placebo vial will be administered intravenously alongside carboprost and intramuscularly alongside oxytocin in order to conserve the blinding of treatments for both healthcare professionals and participants. This will eradicate any potential bias. The design of this study has been developed to have minimal impact on families, resulting in the need for no extra clinic visits within the trial. Clinical outcome data will be collected from medical records. Each participant will be followed up at 24 hours and 4 weeks post randomisation to obtain data for the childbirth experience questionnaire, and information regarding their resource use and quality of life, where applicable. Such follow-up documents will be paper based and posted to the homes of participating women for their completion. At the time of consent to the main study, participants will also be invited to take part in an embedded study, including; 1. Audio recording of COPE antenatal consent discussions between women and their birth partner (if applicable) and trial recruiters 2. Interviews with women and their birth partners (if applicable) who agree or decline consent including bereaved women; either by telephone or at an agreed location 3. A questionnaire for both women who agree or decline consent to the main trial 4. Focus groups and/or interviews with COPE trial recruiters at each pilot site |
| Intervention type | Other |
| Primary outcome measure | Blood transfusion - any RBC blood transfusion or cell salvage of ≥ 300ml commenced any time between randomisation and 48 hours after randomisation (or hospital discharge if earlier than 48 hrs), measured using medical notes |
| Secondary outcome measures | 1. Volume of blood transfusion from randomisation up to 48 hours (or hospital discharge if earlier), measured using medical notes 2. Use of a further uterotonic drug from randomisation up to 24 hours after randomisation, measured using medical notes 3. Composite outcome of any organ dysfunction based on WHO near-miss approach for maternal health (2) from randomisation up to hospital discharge (or 4 weeks whichever is earlier) 4. Hysterectomy from randomisation up to hospital discharge (or 4 weeks whichever is earlier) , measured using medical notes 5. Blood loss in ml commencing in the first 24 hours from randomisation, up to cessation of active bleeding, measured using medical notes 6. Blood loss ≥ 1000 ml, measured using medical notes 7. Haemoglobin closest to 24 hours after randomisation, measured using medical notes 8. Shock within 24 hours of randomisation, measured using medical notes 9. Maternal death within 4 weeks of the birth where postpartum haemorrhage was a contributing factor (it does not need to be the primary cause), measured using medical notes 10. Non pharmacological approach to treat or investigate bleeding from randomisation up to hospital discharge, measured using medical notes 11. Manual removal of placenta post randomisation up to hospital discharge, measured using medical notes 12. Any adverse reactions of the intervention for the mother (hypotension occurring within 2 mins of IMP administration, all other adverse reactions occurring within 2 hrs of administration) , measured using medical notes 13. ‘Skin to skin’ care with baby within the first hour after birth, measured using medical notes 14. Separation from new-born in first hour after birth, measured using medical notes 15. Breastfeeding, measured using [method] at 24 hrs, 48 hrs (or hospital discharge if sooner) and 4 weeks 16. Woman’s experience, measured using Childbirth Experience Questionnaire (CEQ) at 4 weeks 17. Resource use, measured using EQ-5D-5L, resource use questionnaire and hospital episode statistics at 24 hrs and 4 weeks |
| Overall study start date | 01/09/2017 |
| Overall study end date | 28/11/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 2000; UK Sample Size: 2000 |
| Participant inclusion criteria | 1. ≥16 years of age 2. Requirement for medical treatment for primary PPH |
| Participant exclusion criteria | Current participant exclusion criteria as of 28/03/2025: 1. Known to have opted out of participation antenatally 2. Known oxytocin or carboprost hypersensitivity 3. Known active cardiac or pulmonary disease 4. Known to have previously been treated as part of COPE 5. Has already received carboprost prophylactically for postpartum haemorrhage 6. Has already received uterotonic drug treatment for postpartum haemorrhage (this does not include PPH prophylaxis) 7. Stillbirth Previous participant exclusion criteria: 1. Known to have opted out of participation antenatally 2. Known oxytocin or carboprost hypersensitivity 3. Known active cardiac or pulmonary disease 4. Known to have previously been treated as part of COPE 5. Has already received uterotonic drug treatment for postpartum haemorrhage (this does not include PPH prophylaxis) 6. Stillbirth |
| Recruitment start date | 01/11/2020 |
| Recruitment end date | 31/05/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Liverpool
L8 7SS
United Kingdom
Edgbaston
Birmingham
B15 2TG
United Kingdom
Sunderland
SR4 7TP
United Kingdom
London
NW1 2BU
United Kingdom
Burnley
BB10 2PQ
United Kingdom
Kingston upon Thames
KT2 7QB
United Kingdom
Newcastle upon Tyne
TS1 4LP
United Kingdom
Stockton-on-tees
TS19 8PE
United Kingdom
Magdala Avenue
London
N19 5NF
United Kingdom
Sherriff Hill
Gateshead
NE9 6SX
United Kingdom
Windmill Road
Gillingham
ME7 5NY
United Kingdom
Longfleet Road
Poole
BH15 2JB
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom
Orpington
BR6 8ND
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Carmarthen
SA31 2AF
United Kingdom
Rake Lane
North Shields
NE29 8NH
United Kingdom
Taunton
TA1 5DA
United Kingdom
Sponsor information
University/education
c/o Mr Alex Astor
Address Research Support Office
2nd Floor Block D Waterhouse Building
3 Brownlow Street
Liverpool
L69 3GL
England
United Kingdom
| Phone | +44 (0)1517948739 |
|---|---|
| sponsor@liverpool.ac.uk | |
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 28/05/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository, Available on request |
| Publication and dissemination plan | Protocol will be made available at a later date. Planned publication of the results in a high-impact peer reviewed journal. |
| IPD sharing plan | 1. The datasets generated during and/or analysed during the current study will be stored in a non-publicly available repository 2. The datasets generated during and/or analysed during the current study are/will be available upon request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version v2.0 | 26/09/2018 | 02/04/2019 | No | Yes |
| Participant information sheet | version v2.0 | 26/09/2018 | 02/04/2019 | No | Yes |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | version 9.0 | 05/03/2024 | 28/03/2025 | No | Yes |
| Protocol file | version 8.0 | 06/03/2024 | 28/03/2025 | No | No |
Additional files
Editorial Notes
07/04/2025: The study hypothesis and interventions were amended, and the target number of participants changed from "Planned Sample Size: 3948; UK Sample Size: 3948".
28/03/2025: The following changes were made:
1. Protocol (not peer-reviewed) and participant information sheet version 9.0 uploaded.
2. The participant exclusion criteria were updated.
12/02/2024: IPD sharing plan added.
09/02/2024: The following changes were made to the trial record:
1. The recruitment end date was changed from 28/02/2024 to 31/05/2025.
2. The overall end date was changed from 31/03/2024 to 28/11/2025.
3. The intention to publish date was changed from 30/09/2024 to 28/05/2026.
25/08/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/03/2022 to 28/02/2024.
2. The overall end date was changed from 31/12/2022 to 31/03/2024.
3. The intention to publish date was changed from 01/07/2023 to 30/09/2024.
4. The plain English summary was updated to reflect these changes.
5. The IRAS number was added.
6. The study participating centre St Thomas Hospital was removed and Burnley General Hospital, Kingston Hospital, The Royal Victoria Infirmary, University Hospital of North Tees, Whittington Health NHS Trust, Gateshead Hospitals NHS Trust, Medway NHS Foundation Trust, Poole Hospital, John Radcliffe Hospital, Nottingham University Hospitals NHS Trust - City Campus, Kings College Hospital, Princess Royal University Hospital, Queens Medical Centre, Nottingham University Hospital, West Wales General Hospital, North Tyneside General Hospital, Musgrove Park Hospital were added.
12/10/2020: The following changes have been made:
1. The recruitment start date has been changed from 01/12/2018 to 01/11/2020.
2. The recruitment end date has been changed from 01/12/2020 to 31/03/2022.
3. The overall trial start date has been changed from 01/09/2018 to 01/09/2017.
4. The overall trial end date has been changed from 01/09/2021 to 31/12/2022.
5. The intention to publish date has been changed from 01/09/2022 to 01/07/2023.
6. The plain English summary has been updated accordingly.
7. The scientific contact's address has been updated.
02/04/2019: The participant information sheet has been uploaded.
25/03/2019: The condition has been changed from "Specialty: Reproductive Health and Childbirth, Primary sub-specialty: Intrapartum Care; Health Category: Reproductive health and childbirth; Disease/Condition: Complications of labour and delivery" to "Postpartum haemorrhage" following a request from the NIHR.
18/10/2018: The participant information sheet has been uploaded.
