Clinical trial NCT05598502: REBOA in Life-threatening Postpartum Hemorrhage (PPH) in Uganda
Official title: A Phase III, Open-label, Randomized Clinical Trial to Evaluate Efficacy and Safety of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in Life-threatening Postpartum Hemorrhage in Reducing Adverse Maternal Outcome in Uganda
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Post-partum Hemorrhage
Keywords: REBOA
Resuscitative Endovascular Occlusion of the Aorta
Lead sponsor: Centre For International Health
Sponsor class: OTHER
Collaborators: name: Makerere University
name: Kawempe National Referral Hospital
name: St. Olavs Hospital
name: Helse Stavanger HF
name: University of Liverpool
name: University of Padova
First posted: 2022-10-28
Enrollment: 95
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Individual randomization
Primary purpose: TREATMENT

Brief summary: Background Maternal mortality rates in many low-income countries (LMICs) remain high. The most prominent cause is bleeding after birth, called postpartum haemorrhage (PPH). In a recent report from Uganda, bleeding is the cause of 42% of all maternal deaths in Uganda.

Large parts of the monitoring of mothers during active management of third stage of labour is aiming to prevent and early detect PPH and take relevant actions. In spite of this and sometimes in referring mothers to tertiary hospitals, mothers will end up in a challenging condition where quick action is needed. A new method has proven successful for such instances, the Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). This is a procedure commonly used for trauma of the lower part of the body but rarely used for PPH. A balloon catheter is inserted via the femoral artery in the groin into the aorta and then being inflated. This will prevent blood from passing to the lower part of the body, including the uterus. It will stop the bleeding and allow for the obstetrician to take relevant action. This is a safe procedure for up to 1 hour of balloon occlusion time including repeated short balloon deflations.

Objective To assess the efficacy and safety of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in life-threatening postpartum haemorrhage (PPH) in reducing adverse maternal outcome compared to standard of care in Uganda.

Study design, setting and population A phase IIb/III, open label, 1:1 randomized clinical trial will be conducted at Kawempe National Referral Hospital, Kampala, Uganda, to evaluate the efficacy and safety of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in life-threatening postpartum haemorrhage (PPH) in reducing adverse maternal outcome compared to standard of care. The inclusion criteria are: a) women with life-threatening PPH and a systolic blood pressure equal to or less than 80 mmHg, b) written consent. The exclusion criterion is prior cardiac arrest or intra-abdominal pregnancy. The sample size of the trial will be 212 participants. Enrolment will follow a group sequential design approach with two interim analyses at 50% and 85% of the total sample size, and a final analysis with full sample size.

Utility of the study It is crucial to explore alternative modalities that could prevent adverse maternal outcomes in life-threatening postpartum haemorrhage in Uganda and the rest of the world.

Detailed description: Background

Maternal mortality rates in many low-income countries (LMICs) remain high. The most prominent cause is bleeding after birth, called postpartum hemorrhage (PPH). In a recent report from Uganda, bleeding is the cause of 42% of all maternal deaths in Uganda.

Large parts of the monitoring of mothers during active management of third stage of labor is aiming to prevent and early detect PPH and take relevant actions. In spite of this and sometimes in referring mothers to tertiary hospitals, mothers will end up in a challenging condition where quick action is needed. A new method has proven successful for such instances, the Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). This is a procedure commonly used for trauma of the lower part of the body but rarely used for PPH. In this trial, it is done by an anesthesiologist where a balloon catheter is inserted via the femoral artery in the groin into the aorta and then being inflated. This will prevent blood from passing to the lower part of the body, including the uterus. It will stop the bleeding and allow for the obstetrician to take relevant action. This is a safe procedure for up to 1 hour of inflation.

Objective

To assess the efficacy and safety of the use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in life-threatening postpartum hemorrhage (PPH) in reducing adverse maternal outcome compared to standard of care in Uganda.

Primary objectives

* To assess if the proportion of participants with either maternal death and/or emergency hysterectomy, can be decreased from 50 % in the comparator arm (using standard of care alone) to 30 % or less in the intervention arm (using standard of care plus REBOA).
* To assess the safety of REBOA in a national referral hospital in a low-income country like Uganda.

Secondary objectives

* To assess if the proportion of participants with either maternal death and/or emergency hysterectomy is lower in the intervention arm when excluding 'inevitable' hysterectomies due to either an irreparable uterine rupture, a pathological placenta growing into the uterus (placenta accreta, increta or percreta) or a pathological uterus, such as a bicorne uterus or one with very large fibroids.
* To assess if the proportion of participants with maternal deaths is lower in the intervention arm compared to the comparator arm.
* To assess if the proportion of participants with emergency hysterectomy, is lower in the intervention arm compared to the comparator arm.
* To assess if the number of participants with acute kidney injury 35is lower in the intervention arm compared to the comparator arm
* To assess if the number of blood transfusion units is lower in the intervention arm compared to the comparator arm.
* To assess if post-partum haemoglobin concentration is higher in in the intervention arm compared to the comparator arm.
* To assess the time to insert the REBOA.

Study design, setting and population The trial design will be a seamless phase IIb/III study. The study will start with a phase IIb study where the focus is on assessing the safety of REBOA use in a national referral hospital in a low-income country like Uganda. In this phase there will be 10 participants recruited consecutively to intervention arm (REBOA) without randomisation. The aim of the pilot phase is to demonstrate that the REBOA procedure is safe and feasible in the patient cohort.

The phase III trial is a randomised, controlled, open-label, superiority trial among women with life-threatening post-partum haemorrhage with two parallel arms and a primary endpoint of either death or hysterectomy. Individual randomisation will be performed as block randomization with a 1:1 allocation.

The trial will be conducted at Kawempe National Referral Hospital, Kampala, Uganda.

The sample size of the trial will be 212 participants. Enrolment will follow a group sequential design approach with two interim analyses at 1/2 and 85% of the total sample size, and a final analysis with full sample size.

Results from Norway indicate that REBOA could be an efficient way to prevent post-partum hemorrhage ending in an adverse outcome such as death or emergency hysterectomy. It is not clear whether these results can be reproduced in a low-income setting where PPH is more prevalent, and resources are scarce. The REBOA device could reduce the risk of adverse outcome such as death or emergency hysterectomy. It will be compared to standard of care.

Utility of the study

It is crucial to explore alternative modalities that could prevent adverse maternal outcomes in life-threatening postpartum hemorrhage in Uganda and the rest of the world.

Eligibility criteria: Inclusion Criteria:

* Patients with life-threatening PPH, defined as either:

  1. Ongoing PPH and a systolic blood pressure equal to or less than 80 mm Hg, or
  2. Ongoing PPH, a systolic blood pressure equal to or less than 90 mg Hg and the administration of vasoactive drugs, or
  3. Ongoing PPH and a systolic blood pressure equal to or less than 90 mg Hg as well as a pulse greater than or equal to 120 beats per minute recorded simultaneously

and

* Consent, Deferred consent since 3rd September 2024

Exclusion Criteria:

* Prior cardiac arrest
* Intra-abdominal pregnancy

Primary outcomes:
measure: Adverse outcome
timeFrame: 42 days
Secondary outcomes:
measure: Adverse outcome excluding 'inevitable' hysterectomies
timeFrame: 42 days
measure: Number of AEs and SAEs
timeFrame: 42 days
measure: Maternal death
timeFrame: 42 days
measure: Emergency hysterectomy
timeFrame: 42 days
measure: Acute kidney injury
timeFrame: 42 days
measure: Transfusions
timeFrame: 42 days
measure: Hemoglobin
timeFrame: 42 days
Other outcomes:
measure: REBOA insertion time
timeFrame: 1 day
Locations:
city: Kampala
country: Uganda
facility: Kawempe National Referral Hospital
Study officials:
affiliation: University of Bergen, Norway
name: Thorkild Tylleskar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stensaeth KH, Sovik E, Haig IN, Skomedal E, Jorgensen A. Fluoroscopy-free Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for controlling life threatening postpartum hemorrhage. PLoS One. 2017 Mar 29;12(3):e0174520. doi: 10.1371/journal.pone.0174520. eCollection 2017.
citation: Webster LA, Little O, Villalobos A, Nguyen J, Nezami N, Lilly M, Dariushnia S, Gandhi R, Kokabi N. REBOA: Expanding Applications From Traumatic Hemorrhage to Obstetrics and Cardiopulmonary Resuscitation, From the AJR Special Series on Emergency Radiology. AJR Am J Roentgenol. 2023 Jan;220(1):16-22. doi: 10.2214/AJR.22.27932. Epub 2022 Aug 3.
citation: Brede JR, Sovik E, Rehn M. Resuscitative endovascular balloon occlusion of the aorta: the postpartum haemorrhage perspective. Crit Care. 2022 Mar 11;26(1):57. doi: 10.1186/s13054-022-03942-0. No abstract available.
citation: Brede JR, Rehn M. The end of balloons? Our take on the UK-REBOA trial. Scand J Trauma Resusc Emerg Med. 2023 Oct 31;31(1):69. doi: 10.1186/s13049-023-01142-5.