Post-Partum HaemorrhageE-MOTIVENCT04341662
A Clinical Trial to Study the Effectiveness of a Care Bundle to Prevent Bleeding After a Woman Has Given Birth
A study testing E-MOTIVE intervention in people with Post-Partum Haemorrhage, run by University of Birmingham at 6 sites in 5 countries.
Trial summary
Every six minutes a mother dies from postpartum haemorrhage (PPH) in low-resource countries, in the prime of her life and often leaving behind a young family. In many settings, when a mother dies in childbirth, her infant has less than a 20% chance of surviving past the first month. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Post-Partum Haemorrhage
- What is being tested?
- E-MOTIVE intervention
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99,659 participants
- Where
- 6 sitesin 5 countries
- Study dates
- 13 Oct 2020to 24 Mar 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Cluster: Health facility is the randomisation unit. Health facilities are eligible for inclusion if they have 1000 to 5000 births a year and provide comprehensive obstetric care with ability to perform surgery for PPH. Health facilities are selected based on being administratively and geographically distinct from each other. Pre-existing implementation of early detection or bundled approach are exclusion criteria
Research participants: All healthcare providers attending vaginal births at the study facilities.
Patients: All verified vaginal births in the study facilities
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
South Africa2 sites
University of Cape Town
Cape Town
University of the Witwatersrand
Johannesburg
Tanzania1 site
Muhimbili University of Health and Allied Sciences
Dar es Salaam
About this study
Official title: Early Detection of Postpartum Haemorrhage and Treatment Using the World Health Organisation MOTIVE 'First Response' Bundle: a Cluster Randomised Trial With Health Economic Analysis and Mixed-methods Evaluation (E-MOTIVE Trial)
Every six minutes a mother dies from postpartum haemorrhage (PPH) in low-resource countries, in the prime of her life and often leaving behind a young family. In many settings, when a mother dies in childbirth, her infant has less than a 20% chance of surviving past the first month. PPH, defined as a blood loss of more than 500 ml, is the leading cause of maternal death worldwide, accounting for 27% of maternal deaths. The WHO published "Recommendations for the Prevention and Treatment of Postpartum Hemorrhage" in 2012 to provide evidence-informed recommendations for managing PPH. However, adherence to these recommendations is currently limited by a number of challenges.
This primary aim of this multi-country, parallel cluster randomised trial with a baseline control phase, along with mixed-methods and health economic evaluations, is to evaluate the implementation of early detection and the use of the World Health Organisation (WHO) MOTIVE 'first response' treatment bundle for postpartum haemorrhage (PPH) on clinical, implementation and resource use outcomes. The investigators will evaluate the implementation through mixed-methods and carry out a health economic evaluation from the public healthcare system perspective.
Read the detailed description
The aim of this trial is evaluate the implementation of early detection and the use of the WHO MOTIVE 'first response' treatment bundle for PPH on clinical, implementation and resource use outcomes. The investigators will evaluate the implementation through mixed-methods and carry out a health economic evaluation from the public healthcare system perspective. The investigators will use a multi-country, parallel cluster randomised trial design with a baseline control phase, along with mixed-methods and health economic evaluations. The trial is conducted in secondary level health facilities in four low- and middle- income countries. For this trial, the health facility is the randomisation unit. Health facilities are eligible for inclusion if they have 1000 to 5000 births a year and provide comprehensive obstetric care with ability to perform surgery for PPH. Pre-existing implementation of early detection or bundled approach are exclusion criteria. The research participants are all healthcare providers attending vaginal births in the study facilities. The E-MOTIVE intervention consists of three elements: 1) a strategy for early detection of PPH, which allows triggering of the 'first response' treatment bundle; 2) a 'first response' bundle called "MOTIVE", based on the WHO guideline recommendations and consisting of uterine Massage, Oxytocic drugs, Tranexamic acid, IV fluids and Examination \& Escalation; and 3) an implementation strategy, focusing on simulation-based training with peer-assisted learning, local E-MOTIVE champions, feedback of actionable data to providers, calibrated drape with trigger line, and MOTIVE emergency trolley and/or carry case. The control health facilities will deliver usual care with dissemination of the current guidelines.
The primary outcome is a composite of the following three clinical outcomes: 1) primary severe PPH defined as blood loss ≥1000 ml following a vaginal birth in the facility measured up to 2 hours postpartum; 2) postpartum laparotomy for bleeding until discharge from the health facility; and 3) postpartum maternal death from bleeding until discharge from the health facility. If any of the components occur, this will be deemed as positive for the primary outcome.
The key secondary implementation outcomes of special interest are 1) PPH detection (with the following numerator and denominator: women who objectively had PPH (source-verified blood loss ≥ 500 mL after weighing of the drape) and were diagnosed with PPH by the birth attendants divided by the total number of women who objectively had PPH (source verified blood loss ≥ 500 mL after weighing the drape), and 2) compliance with MOTIVE bundle (with the following numerator and denominator: women who objectively had PPH and were treated with the PPH bundle following a diagnosis of PPH by the birth attendants divided by the total number of women who objectively had PPH (blood loss ≥ 500 mL after weighing of the drape).
Secondary outcomes: blood transfusion, uterine tamponade, Intensive Care Unit admissions or higher-level facility transfers, and new-born deaths along with implementation and resource use outcomes.
Eighty health facilities will take part in the study. Initially, all health facilities will enter a 7-month baseline period in which they will be following usual care. After this, we will randomise 40 of the 80 health facilities to the E-MOTIVE intervention for 7 months, allowing two months for transition. The other 40 health facilities will continue to follow usual care as per the baseline period for the entire trial duration (16 months). The anticipated sample size for the study will be 215,040 women. This sample size is expected to have over 90% power to detect a 25% relative reduction in the primary outcome from 4% to 3% after allowing for clustering. The number of clusters has been inflated by 10% to allow for drop out of health facilities and for varying cluster sizes. Randomisation will use a minimisation algorithm to balance the intervention and control facilities by the number of vaginal births per health facility, the health facility rate of the composite primary outcome during the baseline phase, the quality of oxytocin used per health facility, and the number of facilities in each arm.
During the 7-month baseline phase, the investigators will refine and optimise the E-MOTIVE implementation strategy by piloting it in two to three facilities per country over up to two adaptive cycles for addressing barriers and enablers to delivery and implementation, ahead of the intervention phase.
The investigators will also conduct a mixed-methods process evaluation to assess the extent to which the E-MOTIVE intervention has been implemented as intended. The implementation outcomes of interest are fidelity, adoption, adaptation, acceptability, and sustainability, as well as contextual influences and barriers and enablers to implementation.
The investigators plan to assess the cost-effectiveness of the E-MOTIVE intervention compared with usual care from a public healthcare system perspective for each country, as measured by incremental cost-effectiveness ratios for a) severe PPH prevented, b) laparotomy for PPH prevented, c) death from PPH avoided, and (d) quality-adjusted life-years prevented.
Following the publication of the E-MOTIVE trial findings, a prospective pre-post intervention study of the E-MOTIVE intervention was planned in eight secondary-level care District Head Quarter (DHQ) hospitals in the Sindh and Punjab provinces of Pakistan. Pakistan was originally scheduled to be part of the multi-country, cluster-randomised E-MOTIVE trial. However, the catastrophic floods in Pakistan in 2022 delayed the start of recruitment, whilst the other participating countries progressed to complete the trial. At this stage, as the required sample size for the trial had been achieved, the Independent Data Monitoring Committee advised completing and analysing the trial without the participation of Pakistan. The definitive effects found by the E-MOTIVE trial made it unethical to conduct further randomised trials of the intervention. As all countries that contributed to the E-MOTIVE trial were from Africa, an outstanding question on generalisability of the findings outside of Africa remained. The E-MOTIVE study in Pakistan was, therefore, planned as a pre-post study to assess the implementation and generalisability of E-MOTIVE in a South Asian healthcare setting. The amended protocol was approved by the University of Birmingham, UK and the Pakistan ethics and regulatory review committee. The study retained the same primary clinical and implementation outcomes as the main trial.
- Conditions
- Post-Partum Haemorrhage
- Being tested
- E-MOTIVE intervention, Usual care
- Keywords
- post-partum haemorrhage, early detection, blood loss measurement, oxytocin, tranexamic acid
- Medical subject headings
- Postpartum Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E-MOTIVE interventionBehavioural
The E-MOTIVE intervention consists of three elements: 1) a strategy for early detection of PPH, which allows triggering of the 'first response' treatment bundle; 2) a 'first response' bundle called "MOTIVE", based on the WHO guideline recommendations and consisting of uterine Massage, Oxytocic drugs, Tranexamic acid, IV fluids and Examination \& Escalation; and 3) an implementation strategy, focusing on simulation-based training with peer-assisted learning, local E-MOTIVE champions, feedback of actionable data to providers, calibrated drape with trigger line, and MOTIVE emergency trolley and/or carry case.
Usual careBehavioural
Health facilities will continue to follow usual care as per the baseline period for the remainder of the intervention phase.
| Study group | Role | What they receive |
|---|---|---|
| E-MOTIVE intervention | Experimental | The E-MOTIVE intervention consists of three elements: 1) a strategy for early detection of PPH, which allows triggering of the 'first response' treatment bundle; 2) a 'first response' bundle called "MOTIVE", based on the WHO guideline recommendations and consisting of uterine Massage, Oxytocic drugs, Tranexamic acid, IV fluids and Examination \& Escalation; and 3) an implementation strategy, focusing on simulation-based training with peer-assisted learning, local E-MOTIVE champions, feedback of actionable data to providers, calibrated drape with trigger line, and MOTIVE emergency trolley and/or carry case. Receives: Behavioral: E-MOTIVE intervention |
| Usual care | Active comparator | Usual care with dissemination of the current guidelines Receives: Behavioral: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Outcome is a Composite of the Following Three Clinical Outcomes: 1) Severe PPH Defined as Blood Loss ≥1000 ml or; 2) Postpartum Laparotomy for Bleeding or; 3) Postpartum Maternal Death From Bleeding. Please See Below for Further Details.
- Number of women with primary severe PPH defined as blood loss ≥1000 ml following a vaginal birth in the facility up to 2 hours postpartum
- Number of women with postpartum laparotomy for bleeding until discharge from the health facility
- Number of postpartum maternal deaths from bleeding until discharge from the health facility.
A Blinded Endpoint Review Committee (BERC) will assess incoming data relevant to the primary outcome in order to confirm if any postpartum laparotomy was performed for bleeding and if any maternal death was due to bleeding
Measured: Postpartum until discharge from the health facility (up to 42 days)
Secondary outcomes (33)
PPH Detection
With the following numerator and denominator: women who objectively had PPH (source-verified blood loss ≥ 500 mL after weighing of the drape) and were diagnosed with PPH by the birth attendants divided by the total number of women who objectively had PPH (source verified blood loss ≥ 500 mL after weighing the drape)
Measured: Up to 24 hours postpartum
Compliance With MOTIVE Bundle
Defined as adherence with three core elements of the bundle: administration of oxytocic drugs, TXA and IV fluids. If all three core elements are administered when a PPH is diagnosed, this will be deemed positive for bundle compliance
Measured: Up to 24 hours postpartum
Number of Women With Laparotomy Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days)
Number of Women With Laparotomy With Compression Sutures Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women With Laparotomy With Arterial Ligation Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the healthcare facility (up to 42 days).
Number of Women With Hysterectomy Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women With Hysterectomy for Bleeding Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Rate of All Cause Maternal Mortality Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Amount of Blood Loss (as a Continuous Variable)
Reported in millilitres
Measured: Up to 24 hours postpartum
Number of Women With Primary PPH Defined as Blood Loss ≥500 ml
Measured in mililitres
Measured: Up to 24 hours postpartum
Duration of Hospitalisation Postpartum
Measured in days
Measured: Postpartum until discharge from the health facility (up to 42 days).
Duration of ICU Hospitalisation Postpartum
Measured in days
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Transferred to a Higher-level Facility Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Rate of All Cause Neonatal Mortality Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Receiving Non-pneumatic Anti-shock Garment (NASG) Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Receiving Uterine Balloon Tamponade Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Receiving a Blood Transfusion Postpartum Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Receiving Blood Transfusion for Postpartum Haemorrhage Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Admitted to Intensive Care Unit (ICU) Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Number of Women With Primary Severe PPH (Defined as Blood Loss ≥1000 ml) Following a Vaginal Birth in the Facility Measured up to 2 Hours Postpartum
Measured: Up to 2 hours postpartum
Postpartum Laparotomy for Bleeding Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
Postpartum Maternal Death From Bleeding Until Discharge From the Health Facility
Measured: Postpartum until discharge from the health facility (up to 42 days).
PPH Treatment by Healthcare Provider up to 2 Hours Postpartum (or up to 24 Hours if Bleeding Continues)
With the following numerator and denominator: women diagnosed with PPH by the birth attendants divided by the total of women having a vaginal birth in the health facility
Measured: Up to 2 hours postpartum (or up to 24 hours if bleeding continues)
Bundle Usage up to 2 Hours Postpartum (or up to 24 Hours if Bleeding Continues)
With the following numerator and denominator: women treated with the PPH bundle following a diagnosis of PPH by the birth attendants divided by the total of women having a vaginal birth in the health facility
Measured: Up to 2 hours postpartum (or up to 24 hours if bleeding continues)
Bundle Usage for PPH up to 2 Hours Postpartum (or up to 24 Hours if Bleeding Continues)
With the following numerator and denominator: women treated with the PPH bundle following a diagnosis of PPH by the birth attendant divided by the total of women diagnosed with PPH by the birth attendants
Measured: Up to 2 hours postpartum (or up to 24 hours if bleeding continues)
Number of Women Receiving Uterine Massage for PPH
Measured: Up to 24 hours postpartum
Number of Women Receiving Oxytocin for PPH
Measured: Up to 24 hours postpartum
Number of Women Receiving Misoprostol for PPH
Measured: Up to 24 hours postpartum
Number of Women Receiving TXA for PPH
Measured: Up to 24 hours postpartum
Number of Women Receiving Intravenous Fluids (IV) for PPH
Measured: Up to 24 hours postpartum
Number of Women Receiving Examination of the Genital Tract
Physical observation (no specific tool used).
Measured: Up to 24 hours postpartum
Number of Women Receiving Any Treatment Uterotonic for PPH
Measured: Up to 24 hours postpartum
Number of Women Requiring Additional Treatment Interventions (Not Responding to the MOTIVE Bundle).
Measured: Up to 24 hours postpartum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2020
- Study start13 Oct 2020
- Primary completion24 Mar 2023
- Study completion24 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Post-Partum HaemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel cluster randomised trial with a baseline control phase, along with mixed-methods and health economic evaluations
- Masking
- None (open label)
- Enrolment
- 99,659 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London, University of Melbourne, University of California, World Health Organization, King's College London, University of Liverpool, Jhpiego, Concept Foundation, University of Nairobi, University of Cape Town, Bayero University Kano, Nigeria, Muhimbili University of Health and Allied Sciences, University of Witwatersrand, South Africa, Ammalife, Aga Khan University
- Responsible party
- Sponsor
- Investigators
- Arri Coomarasamy, MD, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04341662
- Sponsor's protocol ID
- RG_19-231
- Other IDs
- PACTR202002791391791
- Acronym
- E-MOTIVE
- Status last verified
- Mar 2025
- First submitted
- 7 Feb 2020
- Last updated
- 18 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected IPD
Publications
Gallos I, Devall A, Martin J, Middleton L, Beeson L, Galadanci H, Alwy Al-Beity F, Qureshi Z, Hofmeyr GJ, Moran N, Fawcus S, Sheikh L, Gwako G, Osoti A, Aswat A, Mammoliti KM, Sindhu KN, Podesek M, Horne I, Timms R, Yunas I, Okore J, Singata-Madliki M, Arends E, Wakili AA, Mwampashi A, Nausheen S, Muhammad S, Latthe P, Evans C, Akter S, Forbes G, Lissauer D, Meher S, Weeks A, Shennan A, Ammerdorffer A, Williams E, Roberts T, Widmer M, Oladapo OT, Lorencatto F, Bohren MA, Miller S, Althabe F, Gulmezoglu M, Smith JM, Hemming K, Coomarasamy A. Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage. N Engl J Med. 2023 Jul 6;389(1):11-21. doi: 10.1056/NEJMoa2303966. Epub 2023 May 9.
PubMed 37158447Williams EV, Goranitis I, Oppong R, Perry SJ, Devall AJ, Martin JT, Mammoliti KM, Beeson LE, Sindhu KN, Galadanci H, Alwy Al-Beity F, Qureshi Z, Hofmeyr GJ, Moran N, Fawcus S, Mandondo S, Middleton L, Hemming K, Oladapo OT, Gallos ID, Coomarasamy A, Roberts TE. A cost-effectiveness analysis of early detection and bundled treatment of postpartum hemorrhage alongside the E-MOTIVE trial. Nat Med. 2024 Aug;30(8):2343-2348. doi: 10.1038/s41591-024-03069-5. Epub 2024 Jun 6.
PubMed 38844798Forbes G, Akter S, Miller S, Galadanci H, Qureshi Z, Fawcus S, Hofmeyr GJ, Moran N, Singata-Madliki M, Dankishiya F, Gwako G, Osoti A, Thomas E, Gallos I, Mammoliti KM, Devall A, Coomarasamy A, Althabe F, Atkins L, Bohren MA, Lorencatto F. Factors influencing postpartum haemorrhage detection and management and the implementation of a new postpartum haemorrhage care bundle (E-MOTIVE) in Kenya, Nigeria, and South Africa. Implement Sci. 2023 Jan 11;18(1):1. doi: 10.1186/s13012-022-01253-0.
PubMed 36631821Akter S, Forbes G, Miller S, Galadanci H, Qureshi Z, Fawcus S, Justus Hofmeyr G, Moran N, Singata-Madliki M, Amole TG, Gwako G, Osoti A, Thomas E, Gallos I, Mammoliti KM, Coomarasamy A, Althabe F, Lorencatto F, Bohren MA. Detection and management of postpartum haemorrhage: Qualitative evidence on healthcare providers' knowledge and practices in Kenya, Nigeria, and South Africa. Front Glob Womens Health. 2022 Nov 18;3:1020163. doi: 10.3389/fgwh.2022.1020163. eCollection 2022.
PubMed 36467287Bohren MA, Lorencatto F, Coomarasamy A, Althabe F, Devall AJ, Evans C, Oladapo OT, Lissauer D, Akter S, Forbes G, Thomas E, Galadanci H, Qureshi Z, Fawcus S, Hofmeyr GJ, Al-Beity FA, Kasturiratne A, Kumarendran B, Mammoliti KM, Vogel JP, Gallos I, Miller S. Formative research to design an implementation strategy for a postpartum hemorrhage initial response treatment bundle (E-MOTIVE): study protocol. Reprod Health. 2021 Jul 14;18(1):149. doi: 10.1186/s12978-021-01162-3.
PubMed 34261508
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Postpartum Haemorrhage and Treatment Using the World Health Organisation MOTIVE 'First Response' Bundle: a Cluster Randomised Trial With Health Economic Analysis and Mixed-methods Evaluation (E-MOTIVE Trial)
- ClinicalTrials.gov ID
- NCT04341662
- Acronym / sponsor ID
- E-MOTIVE / RG_19-231
- Conditions
- Post-Partum Haemorrhage
- Keywords
- post-partum haemorrhage, early detection, blood loss measurement, oxytocin, tranexamic acid
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99,659 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- University College, London, University of Melbourne, University of California, World Health Organization, King's College London, University of Liverpool, Jhpiego, Concept Foundation, University of Nairobi, University of Cape Town, Bayero University Kano, Nigeria, Muhimbili University of Health and Allied Sciences, University of Witwatersrand, South Africa, Ammalife, Aga Khan University
- Study start
- 13 Oct 2020 (actual)
- Primary completion
- 24 Mar 2023 (actual)
- Study completion
- 24 Mar 2023 (actual)
- First posted
- 10 Apr 2020 (actual)
- Results
- Posted 6 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Every six minutes a mother dies from postpartum haemorrhage (PPH) in low-resource countries, in the prime of her life and often leaving behind a young family. In many settings, when a mother dies in childbirth, her infant has less than a 20% chance of surviving past the first month. PPH, defined as a blood loss of more than 500 ml, is the leading cause of maternal death worldwide, accounting for 27% of maternal deaths. The WHO published "Recommendations for the Prevention and Treatment of Postpartum Hemorrhage" in 2012 to provide evidence-informed recommendations for managing PPH. However, adherence to these recommendations is currently limited by a number of challenges.
This primary aim of this multi-country, parallel cluster randomised trial with a baseline control phase, along with mixed-methods and health economic evaluations, is to evaluate the implementation of early detection and the use of the World Health Organisation (WHO) MOTIVE 'first response' treatment bundle for postpartum haemorrhage (PPH) on clinical, implementation and resource use outcomes. The investigators will evaluate the implementation through mixed-methods and carry out a health economic evaluation from the public healthcare system perspective.
Detailed description
The aim of this trial is evaluate the implementation of early detection and the use of the WHO MOTIVE 'first response' treatment bundle for PPH on clinical, implementation and resource use outcomes. The investigators will evaluate the implementation through mixed-methods and carry out a health economic evaluation from the public healthcare system perspective. The investigators will use a multi-country, parallel cluster randomised trial design with a baseline control phase, along with mixed-methods and health economic evaluations. The trial is conducted in secondary level health facilities in four low- and middle- income countries. For this trial, the health facility is the randomisation unit. Health facilities are eligible for inclusion if they have 1000 to 5000 births a year and provide comprehensive obstetric care with ability to perform surgery for PPH. Pre-existing implementation of early detection or bundled approach are exclusion criteria. The research participants are all healthcare providers attending vaginal births in the study facilities. The E-MOTIVE intervention consists of three elements: 1) a strategy for early detection of PPH, which allows triggering of the 'first response' treatment bundle; 2) a 'first response' bundle called "MOTIVE", based on the WHO guideline recommendations and consisting of uterine Massage, Oxytocic drugs, Tranexamic acid, IV fluids and Examination \& Escalation; and 3) an implementation strategy, focusing on simulation-based training with peer-assisted learning, local E-MOTIVE champions, feedback of actionable data to providers, calibrated drape with trigger line, and MOTIVE emergency trolley and/or carry case. The control health facilities will deliver usual care with dissemination of the current guidelines.
The primary outcome is a composite of the following three clinical outcomes: 1) primary severe PPH defined as blood loss ≥1000 ml following a vaginal birth in the facility measured up to 2 hours postpartum; 2) postpartum laparotomy for bleeding until discharge from the health facility; and 3) postpartum maternal death from bleeding until discharge from the health facility. If any of the components occur, this will be deemed as positive for the primary outcome.
The key secondary implementation outcomes of special interest are 1) PPH detection (with the following numerator and denominator: women who objectively had PPH (source-verified blood loss ≥ 500 mL after weighing of the drape) and were diagnosed with PPH by the birth attendants divided by the total number of women who objectively had PPH (source verified blood loss ≥ 500 mL after weighing the drape), and 2) compliance with MOTIVE bundle (with the following numerator and denominator: women who objectively had PPH and were treated with the PPH bundle following a diagnosis of PPH by the birth attendants divided by the total number of women who objectively had PPH (blood loss ≥ 500 mL after weighing of the drape).
Secondary outcomes: blood transfusion, uterine tamponade, Intensive Care Unit admissions or higher-level facility transfers, and new-born deaths along with implementation and resource use outcomes.
Eighty health facilities will take part in the study. Initially, all health facilities will enter a 7-month baseline period in which they will be following usual care. After this, we will randomise 40 of the 80 health facilities to the E-MOTIVE intervention for 7 months, allowing two months for transition. The other 40 health facilities will continue to follow usual care as per the baseline period for the entire trial duration (16 months). The anticipated sample size for the study will be 215,040 women. This sample size is expected to have over 90% power to detect a 25% relative reduction in the primary outcome from 4% to 3% after allowing for clustering. The number of clusters has been inflated by 10% to allow for drop out of health facilities and for varying cluster sizes. Randomisation will use a minimisation algorithm to balance the intervention and control facilities by the number of vaginal births per health facility, the health facility rate of the composite primary outcome during the baseline phase, the quality of oxytocin used per health facility, and the number of facilities in each arm.
During the 7-month baseline phase, the investigators will refine and optimise the E-MOTIVE implementation strategy by piloting it in two to three facilities per country over up to two adaptive cycles for addressing barriers and enablers to delivery and implementation, ahead of the intervention phase.
The investigators will also conduct a mixed-methods process evaluation to assess the extent to which the E-MOTIVE intervention has been implemented as intended. The implementation outcomes of interest are fidelity, adoption, adaptation, acceptability, and sustainability, as well as contextual influences and barriers and enablers to implementation.
The investigators plan to assess the cost-effectiveness of the E-MOTIVE intervention compared with usual care from a public healthcare system perspective for each country, as measured by incremental cost-effectiveness ratios for a) severe PPH prevented, b) laparotomy for PPH prevented, c) death from PPH avoided, and (d) quality-adjusted life-years prevented.
Following the publication of the E-MOTIVE trial findings, a prospective pre-post intervention study of the E-MOTIVE intervention was planned in eight secondary-level care District Head Quarter (DHQ) hospitals in the Sindh and Punjab provinces of Pakistan. Pakistan was originally scheduled to be part of the multi-country, cluster-randomised E-MOTIVE trial. However, the catastrophic floods in Pakistan in 2022 delayed the start of recruitment, whilst the other participating countries progressed to complete the trial. At this stage, as the required sample size for the trial had been achieved, the Independent Data Monitoring Committee advised completing and analysing the trial without the participation of Pakistan. The definitive effects found by the E-MOTIVE trial made it unethical to conduct further randomised trials of the intervention. As all countries that contributed to the E-MOTIVE trial were from Africa, an outstanding question on generalisability of the findings outside of Africa remained. The E-MOTIVE study in Pakistan was, therefore, planned as a pre-post study to assess the implementation and generalisability of E-MOTIVE in a South Asian healthcare setting. The amended protocol was approved by the University of Birmingham, UK and the Pakistan ethics and regulatory review committee. The study retained the same primary clinical and implementation outcomes as the main trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Parallel cluster randomised trial with a baseline control phase, along with mixed-methods and health economic evaluations
| Arm | Type | Receives |
|---|---|---|
| E-MOTIVE intervention | Experimental | Behavioral: E-MOTIVE interventionThe E-MOTIVE intervention consists of three elements: 1) a strategy for early detection of PPH, which allows triggering of the 'first response' treatment bundle; 2) a 'first response' bundle called "MOTIVE", based on the WHO guideline recommendations and consisting of uterine Massage, Oxytocic drugs, Tranexamic acid, IV fluids and Examination \& Escalation; and 3) an implementation strategy, focusing on simulation-based training with peer-assisted learning, local E-MOTIVE champions, feedback of actionable data to providers, calibrated drape with trigger line, and MOTIVE emergency trolley and/or carry case. |
| Usual care | Active comparator | Behavioral: Usual careUsual care with dissemination of the current guidelines |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E-MOTIVE interventionThe E-MOTIVE intervention consists of three elements: 1) a strategy for early detection of PPH, which allows triggering of the 'first response' treatment bundle; 2) a 'first response' bundle called "MOTIVE", based on the WHO guideline recommendations and consisting of uterine Massage, Oxytocic drugs, Tranexamic acid, IV fluids and Examination \& Escalation; and 3) an implementation strategy, focusing on simulation-based training with peer-assisted learning, local E-MOTIVE champions, feedback of actionable data to providers, calibrated drape with trigger line, and MOTIVE emergency trolley and/or carry case. | Behavioural | E-MOTIVE intervention |
| Usual careHealth facilities will continue to follow usual care as per the baseline period for the remainder of the intervention phase. | Behavioural | Usual care |
Primary outcome
The Primary Outcome is a Composite of the Following Three Clinical Outcomes: 1) Severe PPH Defined as Blood Loss ≥1000 ml or; 2) Postpartum Laparotomy for Bleeding or; 3) Postpartum Maternal Death From Bleeding. Please See Below for Further Details.
Time frame: Postpartum until discharge from the health facility (up to 42 days)
1. Number of women with primary severe PPH defined as blood loss ≥1000 ml following a vaginal birth in the facility up to 2 hours postpartum 2. Number of women with postpartum laparotomy for bleeding until discharge from the health facility 3. Number of postpartum maternal deaths from bleeding until discharge from the health facility. A Blinded Endpoint Review Committee (BERC) will assess incoming data relevant to the primary outcome in order to confirm if any postpartum laparotomy was performed for bleeding and if any maternal death was due to bleeding
33 secondary outcomes
PPH Detection
Time frame: Up to 24 hours postpartum
Compliance With MOTIVE Bundle
Time frame: Up to 24 hours postpartum
Number of Women With Laparotomy Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days)
Number of Women With Laparotomy With Compression Sutures Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women With Laparotomy With Arterial Ligation Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the healthcare facility (up to 42 days).
Number of Women With Hysterectomy Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women With Hysterectomy for Bleeding Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Rate of All Cause Maternal Mortality Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Amount of Blood Loss (as a Continuous Variable)
Time frame: Up to 24 hours postpartum
Number of Women With Primary PPH Defined as Blood Loss ≥500 ml
Time frame: Up to 24 hours postpartum
Duration of Hospitalisation Postpartum
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Duration of ICU Hospitalisation Postpartum
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Transferred to a Higher-level Facility Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Rate of All Cause Neonatal Mortality Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Receiving Non-pneumatic Anti-shock Garment (NASG) Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Receiving Uterine Balloon Tamponade Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Receiving a Blood Transfusion Postpartum Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Receiving Blood Transfusion for Postpartum Haemorrhage Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women Admitted to Intensive Care Unit (ICU) Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Number of Women With Primary Severe PPH (Defined as Blood Loss ≥1000 ml) Following a Vaginal Birth in the Facility Measured up to 2 Hours Postpartum
Time frame: Up to 2 hours postpartum
Postpartum Laparotomy for Bleeding Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
Postpartum Maternal Death From Bleeding Until Discharge From the Health Facility
Time frame: Postpartum until discharge from the health facility (up to 42 days).
PPH Treatment by Healthcare Provider up to 2 Hours Postpartum (or up to 24 Hours if Bleeding Continues)
Time frame: Up to 2 hours postpartum (or up to 24 hours if bleeding continues)
Bundle Usage up to 2 Hours Postpartum (or up to 24 Hours if Bleeding Continues)
Time frame: Up to 2 hours postpartum (or up to 24 hours if bleeding continues)
Bundle Usage for PPH up to 2 Hours Postpartum (or up to 24 Hours if Bleeding Continues)
Time frame: Up to 2 hours postpartum (or up to 24 hours if bleeding continues)
Number of Women Receiving Uterine Massage for PPH
Time frame: Up to 24 hours postpartum
Number of Women Receiving Oxytocin for PPH
Time frame: Up to 24 hours postpartum
Number of Women Receiving Misoprostol for PPH
Time frame: Up to 24 hours postpartum
Number of Women Receiving TXA for PPH
Time frame: Up to 24 hours postpartum
Number of Women Receiving Intravenous Fluids (IV) for PPH
Time frame: Up to 24 hours postpartum
Number of Women Receiving Examination of the Genital Tract
Time frame: Up to 24 hours postpartum
Number of Women Receiving Any Treatment Uterotonic for PPH
Time frame: Up to 24 hours postpartum
Number of Women Requiring Additional Treatment Interventions (Not Responding to the MOTIVE Bundle).
Time frame: Up to 24 hours postpartum
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37158447Gallos I, Devall A, Martin J, Middleton L, Beeson L, Galadanci H, Alwy Al-Beity F, Qureshi Z, Hofmeyr GJ, Moran N, Fawcus S, Sheikh L, Gwako G, Osoti A, Aswat A, Mammoliti KM, Sindhu KN, Podesek M, Horne I, Timms R, Yunas I, Okore J, Singata-Madliki M, Arends E, Wakili AA, Mwampashi A, Nausheen S, Muhammad S, Latthe P, Evans C, Akter S, Forbes G, Lissauer D, Meher S, Weeks A, Shennan A, Ammerdorffer A, Williams E, Roberts T, Widmer M, Oladapo OT, Lorencatto F, Bohren MA, Miller S, Althabe F, Gulmezoglu M, Smith JM, Hemming K, Coomarasamy A. Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage. N Engl J Med. 2023 Jul 6;389(1):11-21. doi: 10.1056/NEJMoa2303966. Epub 2023 May 9.
- Derived from this study: PubMed 38844798Williams EV, Goranitis I, Oppong R, Perry SJ, Devall AJ, Martin JT, Mammoliti KM, Beeson LE, Sindhu KN, Galadanci H, Alwy Al-Beity F, Qureshi Z, Hofmeyr GJ, Moran N, Fawcus S, Mandondo S, Middleton L, Hemming K, Oladapo OT, Gallos ID, Coomarasamy A, Roberts TE. A cost-effectiveness analysis of early detection and bundled treatment of postpartum hemorrhage alongside the E-MOTIVE trial. Nat Med. 2024 Aug;30(8):2343-2348. doi: 10.1038/s41591-024-03069-5. Epub 2024 Jun 6.
- Derived from this study: PubMed 36631821Forbes G, Akter S, Miller S, Galadanci H, Qureshi Z, Fawcus S, Hofmeyr GJ, Moran N, Singata-Madliki M, Dankishiya F, Gwako G, Osoti A, Thomas E, Gallos I, Mammoliti KM, Devall A, Coomarasamy A, Althabe F, Atkins L, Bohren MA, Lorencatto F. Factors influencing postpartum haemorrhage detection and management and the implementation of a new postpartum haemorrhage care bundle (E-MOTIVE) in Kenya, Nigeria, and South Africa. Implement Sci. 2023 Jan 11;18(1):1. doi: 10.1186/s13012-022-01253-0.
- Derived from this study: PubMed 36467287Akter S, Forbes G, Miller S, Galadanci H, Qureshi Z, Fawcus S, Justus Hofmeyr G, Moran N, Singata-Madliki M, Amole TG, Gwako G, Osoti A, Thomas E, Gallos I, Mammoliti KM, Coomarasamy A, Althabe F, Lorencatto F, Bohren MA. Detection and management of postpartum haemorrhage: Qualitative evidence on healthcare providers' knowledge and practices in Kenya, Nigeria, and South Africa. Front Glob Womens Health. 2022 Nov 18;3:1020163. doi: 10.3389/fgwh.2022.1020163. eCollection 2022.
- Derived from this study: PubMed 34261508Bohren MA, Lorencatto F, Coomarasamy A, Althabe F, Devall AJ, Evans C, Oladapo OT, Lissauer D, Akter S, Forbes G, Thomas E, Galadanci H, Qureshi Z, Fawcus S, Hofmeyr GJ, Al-Beity FA, Kasturiratne A, Kumarendran B, Mammoliti KM, Vogel JP, Gallos I, Miller S. Formative research to design an implementation strategy for a postpartum hemorrhage initial response treatment bundle (E-MOTIVE): study protocol. Reprod Health. 2021 Jul 14;18(1):149. doi: 10.1186/s12978-021-01162-3.
- Trial websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All collected IPD
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arri Coomarasamy, MD principal investigator
University of Birmingham
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing E-MOTIVE intervention in people with Post-Partum Haemorrhage, run by University of Birmingham at 6 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in South Africa, Kenya, Nigeria, Pakistan, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Primary Outcome is a Composite of the Following Three Clinical Outcomes: 1) Severe PPH Defined as Blood Loss ≥1000 ml or; 2) Postpartum Laparotomy for Bleeding or; 3) Postpartum Maternal Death From Bleeding. Please See Below for Further Details. (time frame: Postpartum until discharge from the health facility (up to 42 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04341662, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2025.