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

NCT ID: NCT04341662

Last Updated: 2025-04-18

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

99659 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-13

Study Completion Date

2023-03-24

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.

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

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Post-Partum Haemorrhage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel cluster randomised trial with a baseline control phase, along with mixed-methods and health economic evaluations
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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E-MOTIVE intervention

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.

Group Type EXPERIMENTAL

E-MOTIVE intervention

Intervention Type BEHAVIORAL

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 care

Usual care with dissemination of the current guidelines

Group Type ACTIVE_COMPARATOR

Usual care

Intervention Type BEHAVIORAL

Health facilities will continue to follow usual care as per the baseline period for the remainder of the intervention phase.

Interventions

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E-MOTIVE intervention

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.

Intervention Type BEHAVIORAL

Usual care

Health facilities will continue to follow usual care as per the baseline period for the remainder of the intervention phase.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Exclusion Criteria

Research participants: All healthcare providers attending vaginal births at the study facilities.

Patients: All verified vaginal births in the study facilities
Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University College, London

OTHER

Sponsor Role collaborator

University of Melbourne

OTHER

Sponsor Role collaborator

University of California

OTHER

Sponsor Role collaborator

World Health Organization

OTHER

Sponsor Role collaborator

King's College London

OTHER

Sponsor Role collaborator

University of Liverpool

OTHER

Sponsor Role collaborator

Jhpiego

OTHER

Sponsor Role collaborator

Concept Foundation

OTHER

Sponsor Role collaborator

University of Nairobi

OTHER

Sponsor Role collaborator

University of Cape Town

OTHER

Sponsor Role collaborator

Bayero University Kano, Nigeria

OTHER

Sponsor Role collaborator

Muhimbili University of Health and Allied Sciences

OTHER

Sponsor Role collaborator

University of Witwatersrand, South Africa

OTHER

Sponsor Role collaborator

Ammalife

INDUSTRY

Sponsor Role collaborator

Aga Khan University

OTHER

Sponsor Role collaborator

University of Birmingham

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arri Coomarasamy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Birmingham

Locations

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University of Nairobi

Nairobi, , Kenya

Site Status

Bayero University

Kano, , Nigeria

Site Status

Aga Khan University

Karachi, , Pakistan

Site Status

University of Cape Town

Cape Town, , South Africa

Site Status

University of the Witwatersrand

Johannesburg, , South Africa

Site Status

Muhimbili University of Health and Allied Sciences

Dar es Salaam, , Tanzania

Site Status

Countries

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Kenya Nigeria Pakistan South Africa Tanzania

References

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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.

Reference Type RESULT
PMID: 37158447 (View on PubMed)

Williams 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.

Reference Type DERIVED
PMID: 38844798 (View on PubMed)

Forbes 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.

Reference Type DERIVED
PMID: 36631821 (View on PubMed)

Akter 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.

Reference Type DERIVED
PMID: 36467287 (View on PubMed)

Bohren 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.

Reference Type DERIVED
PMID: 34261508 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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PACTR202002791391791

Identifier Type: REGISTRY

Identifier Source: secondary_id

RG_19-231

Identifier Type: -

Identifier Source: org_study_id

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