Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE): protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysis
Introduction Excessive bleeding after childbirth (postpartum haemorrhage, PPH) affects 5% of births and causes 75 000 maternal deaths worldwide annually. It is the leading cause of direct maternal deaths globally and continues to be a major cause of mortality in the UK. Oxytocin is the standard firs...
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2025-05-01
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| author | Kerry Woolfall Ben Hardwick Dimitrios Siassakos Andrew Shennan Stephen Robson Dyfrig A Hughes Carrol Gamble Elizabeth Deja Andrew Weeks Peter Collins Jim Thornton Kirtana Vallabhaneni Tina Lavender Gillian Gyte Helen Hickey Egle Saviciute Anna Rosala-Hallas Efstathia Gkioni Kim Hinshaw Catrin Plumpton Shireen Meher Annette L Briley Rachel E Collis Charlotte Van Netten Dilly Anumba Sion Kenyon Elaine Willis |
| author_facet | Kerry Woolfall Ben Hardwick Dimitrios Siassakos Andrew Shennan Stephen Robson Dyfrig A Hughes Carrol Gamble Elizabeth Deja Andrew Weeks Peter Collins Jim Thornton Kirtana Vallabhaneni Tina Lavender Gillian Gyte Helen Hickey Egle Saviciute Anna Rosala-Hallas Efstathia Gkioni Kim Hinshaw Catrin Plumpton Shireen Meher Annette L Briley Rachel E Collis Charlotte Van Netten Dilly Anumba Sion Kenyon Elaine Willis |
| author_sort | Kerry Woolfall |
| collection | DOAJ |
| description | Introduction Excessive bleeding after childbirth (postpartum haemorrhage, PPH) affects 5% of births and causes 75 000 maternal deaths worldwide annually. It is the leading cause of direct maternal deaths globally and continues to be a major cause of mortality in the UK. Oxytocin is the standard first-line treatment for atonic PPH. The PPH rate is increasing, and this may be partially related to the overuse of oxytocics in labour. Laboratory studies on myometrium suggest that repeated use of oxytocics leads to the saturation of oxytocin receptors and reduced therapeutic efficacy of oxytocin. Carboprost (a prostaglandin analogue) is usually reserved for second-line management of atonic PPH. A systematic review comparing the efficacy of carboprost and conventional uterotonics for PPH prophylaxis found that carboprost was associated with less blood loss, but around 15% of women experienced side effects. The study’s aim is to compare intramuscular carboprost with intravenous oxytocin for the initial treatment of PPH. In addition, to assess the cost-effectiveness of both treatments, participants’ views on the two treatments and the consent process.Methods and analysis COPE is a double-blind, double-dummy, randomised controlled trial that aims to recruit 2000 women (1:1 allocation, stratified by mode of birth) across 20 hospitals in the UK. Due to the emergency nature of PPH, COPE uses a research without prior consent (RWPC) model. Randomisation and treatment will occur if eligibility criteria are met once bleeding starts. Postnatal consent will be sought for disclosure of identifiable data and continued follow-up. Clinical efficacy outcomes will be collected at 24 and 48 hours or at hospital discharge, if sooner. Questionnaires will also be collected at 24 hours and 4 weeks postrandomisation. Cost-effectiveness will be based on the incremental cost per quality-adjusted life-year, calculated from the perspective of the NHS and personal social services.Ethics and dissemination This study has been approved by the Coventry and Warwickshire Research Ethics Committee (REC) (18/WM/0227) and the Health Research Authority. Results will be disseminated via peer-reviewed publications.Trial registration number ISRCTN16416766. |
| format | Article |
| id | doaj-art-29e3df69dcfc4670b9217eadaa92edf9 |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-29e3df69dcfc4670b9217eadaa92edf92025-08-20T03:52:52ZengBMJ Publishing GroupBMJ Open2044-60552025-05-0115510.1136/bmjopen-2025-101255Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE): protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysisKerry Woolfall0Ben Hardwick1Dimitrios Siassakos2Andrew Shennan3Stephen Robson4Dyfrig A Hughes5Carrol Gamble6Elizabeth Deja7Andrew Weeks8Peter Collins9Jim Thornton10Kirtana Vallabhaneni11Tina Lavender12Gillian Gyte13Helen Hickey14Egle Saviciute15Anna Rosala-Hallas16Efstathia Gkioni17Kim Hinshaw18Catrin Plumpton19Shireen Meher20Annette L Briley21Rachel E Collis22Charlotte Van Netten23Dilly Anumba24Sion Kenyon25Elaine Willis26Department of Public Health, Policy and Systems, University of Liverpool, Liverpool, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKInstitute for Women’s Health, University College London, London, UKDepartment of Women`s and Children’s Health, King’s College London, London, UKNewcastle University, Newcastle upon Tyne, UKCentre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKDepartment of Public Health, Policy and Systems, University of Liverpool, Liverpool, UKDepartment of Women`s and Children’s Health, University of Liverpool, Liverpool, UKInstitute of Infection and Immunity, Cardiff University, Cardiff, UKObstetrics & Gynaecology, University of Nottingham, Nottingham, UKDepartment of Women`s and Children’s Health, University of Liverpool, Liverpool, UKDepartment of International Public Health, Liverpool School of Tropical Medicine, Liverpool, UKNational Childbirth Trust, London, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKObstetrics and Gynaecology, Sunderland Royal Hospital, Sunderland, UKCentre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UKNepean Clinical School, University of Sydney, Kingswood, New South Wales, AustraliaCaring Futures Institute, Flinders University, Bedford Park, South Australia, AustraliaUniversity Hospital of Wales, Cardiff, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKSchool of Medicine & Population Health, The University of Sheffield, Sheffield, UKLiverpool Clinical Trials Centre, University of Liverpool, Liverpool, UKLiverpool Women’s Hospital NHS Foundation Trust, Liverpool, UKIntroduction Excessive bleeding after childbirth (postpartum haemorrhage, PPH) affects 5% of births and causes 75 000 maternal deaths worldwide annually. It is the leading cause of direct maternal deaths globally and continues to be a major cause of mortality in the UK. Oxytocin is the standard first-line treatment for atonic PPH. The PPH rate is increasing, and this may be partially related to the overuse of oxytocics in labour. Laboratory studies on myometrium suggest that repeated use of oxytocics leads to the saturation of oxytocin receptors and reduced therapeutic efficacy of oxytocin. Carboprost (a prostaglandin analogue) is usually reserved for second-line management of atonic PPH. A systematic review comparing the efficacy of carboprost and conventional uterotonics for PPH prophylaxis found that carboprost was associated with less blood loss, but around 15% of women experienced side effects. The study’s aim is to compare intramuscular carboprost with intravenous oxytocin for the initial treatment of PPH. In addition, to assess the cost-effectiveness of both treatments, participants’ views on the two treatments and the consent process.Methods and analysis COPE is a double-blind, double-dummy, randomised controlled trial that aims to recruit 2000 women (1:1 allocation, stratified by mode of birth) across 20 hospitals in the UK. Due to the emergency nature of PPH, COPE uses a research without prior consent (RWPC) model. Randomisation and treatment will occur if eligibility criteria are met once bleeding starts. Postnatal consent will be sought for disclosure of identifiable data and continued follow-up. Clinical efficacy outcomes will be collected at 24 and 48 hours or at hospital discharge, if sooner. Questionnaires will also be collected at 24 hours and 4 weeks postrandomisation. Cost-effectiveness will be based on the incremental cost per quality-adjusted life-year, calculated from the perspective of the NHS and personal social services.Ethics and dissemination This study has been approved by the Coventry and Warwickshire Research Ethics Committee (REC) (18/WM/0227) and the Health Research Authority. Results will be disseminated via peer-reviewed publications.Trial registration number ISRCTN16416766.https://bmjopen.bmj.com/content/15/5/e101255.full |
| spellingShingle | Kerry Woolfall Ben Hardwick Dimitrios Siassakos Andrew Shennan Stephen Robson Dyfrig A Hughes Carrol Gamble Elizabeth Deja Andrew Weeks Peter Collins Jim Thornton Kirtana Vallabhaneni Tina Lavender Gillian Gyte Helen Hickey Egle Saviciute Anna Rosala-Hallas Efstathia Gkioni Kim Hinshaw Catrin Plumpton Shireen Meher Annette L Briley Rachel E Collis Charlotte Van Netten Dilly Anumba Sion Kenyon Elaine Willis Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE): protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysis BMJ Open |
| title | Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE): protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysis |
| title_full | Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE): protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysis |
| title_fullStr | Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE): protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysis |
| title_full_unstemmed | Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE): protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysis |
| title_short | Carboprost versus Oxytocin as the first-line treatment of primary postpartum haemorrhage (COPE): protocol for a phase IV, double-blind, double-dummy, randomised controlled trial and economic analysis |
| title_sort | carboprost versus oxytocin as the first line treatment of primary postpartum haemorrhage cope protocol for a phase iv double blind double dummy randomised controlled trial and economic analysis |
| url | https://bmjopen.bmj.com/content/15/5/e101255.full |
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