A Clinical Trial to Study the Effectiveness of a Care Bundle to Prevent Bleeding After a Woman Has Given Birth

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Post-Partum Haemorrhage

Intervention / Treatment
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* Behavioral: E-MOTIVE intervention
* Behavioral: Usual care


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel cluster randomised trial with a baseline control phase, along with mixed-methods and health economic evaluations
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E-MOTIVE intervention<br>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. | Behavioral: E-MOTIVE intervention<br>* 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.<br>|
| Active Comparator: Usual care<br>Usual care with dissemination of the current guidelines | Behavioral: Usual care<br>* Health facilities will continue to follow usual care as per the baseline period for the remainder of the intervention phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Postpartum until discharge from the health facility (up to 42 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 | Up to 24 hours postpartum | 
| Number of women with laparotomy postpartum until discharge from the health facility |  | 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 |  | 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 |  | Postpartum until discharge from the healthcare facility (up to 42 days). | 
| Number of women with hysterectomy postpartum until discharge from the health facility |  | 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 |  | Postpartum until discharge from the health facility (up to 42 days). | 
| Rate of all cause maternal mortality postpartum until discharge from the health facility |  | Postpartum until discharge from the health facility (up to 42 days). | 
| Amount of blood loss (as a continuous variable) | Reported in millilitres | Up to 24 hours postpartum | 
| Number of women with primary PPH defined as blood loss ≥500 ml | Measured in mililitres | Up to 24 hours postpartum | 
| Duration of hospitalisation postpartum | Measured in days | Postpartum until discharge from the health facility (up to 42 days). | 
| Duration of ICU hospitalisation postpartum | Measured in days | 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 |  | Postpartum until discharge from the health facility (up to 42 days). | 
| Rate of all cause neonatal mortality postpartum until discharge from the health facility |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | Up to 2 hours postpartum | 
| Postpartum laparotomy for bleeding until discharge from the health facility |  | Postpartum until discharge from the health facility (up to 42 days). | 
| Postpartum maternal death from bleeding until discharge from the health facility |  | 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 | 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 | 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 | Up to 2 hours postpartum (or up to 24 hours if bleeding continues) | 
| Number of women receiving uterine massage for PPH |  | Up to 24 hours postpartum | 
| Number of women receiving Oxytocin for PPH |  | Up to 24 hours postpartum | 
| Number of women receiving Misoprostol for PPH |  | Up to 24 hours postpartum | 
| Number of women receiving TXA for PPH |  | Up to 24 hours postpartum | 
| Number of women receiving Intravenous fluids (IV) for PPH |  | Up to 24 hours postpartum | 
| Number of women receiving examination of the genital tract | Physical observation (no specific tool used). | Up to 24 hours postpartum | 
| Number of women receiving any treatment uterotonic for PPH |  | Up to 24 hours postpartum | 
| Number of women requiring additional treatment interventions (not responding to the MOTIVE bundle). |  | Up to 24 hours postpartum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post-partum haemorrhage, early detection, blood loss measurement, oxytocin, tranexamic acid