Clinical trial NCT05382403: Novel Vacuum-Induced Hemorrhage Control for Postpartum Hemorrhage
Official title: Novel Vacuum-Induced Hemorrhage Control for Postpartum Hemorrhage: a Multicenter Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Postpartum Hemorrhage
Maternal Death
Lead sponsor: Women and Infants Hospital of Rhode Island
Sponsor class: OTHER
Collaborators: name: Washington University School of Medicine
name: University of Ghana
name: Kwame Nkrumah University of Science and Technology
First posted: 2022-05-19
Enrollment: 424
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be the first, definitive, randomized control trial (N=424) to test the hypothesis that the Jada® System is effective, safe and cost-effective in treating PPH, compared to standard care.

Detailed description: Every year, 130 million women deliver babies around the world, and an estimated 14 million (11%) experience postpartum hemorrhage (PPH), recently redefined as a cumulative blood loss of 1000 ml or more or blood loss associated with signs or symptoms of hypovolemia, irrespective of the route of delivery. PPH is the leading cause of maternal mortality worldwide, responsible for 25% of maternal deaths from obstetric causes, with 99% occurring in low and middle income countries (LMICs). Although PPH has multiple causes, the most common is uterine atony when the uterus fails to adequately contract after childbirth, accounting for 70% of all PPH. Active management of the third stage of labor, consisting of administering prophylactic uterotonics, controlled cord traction, and uterine massage after delivery, reduces the incidence of PPH by approximately 66%. These conservative measures facilitate the normal postpartum tetanic myometrial contractions that constrict the placental bed vasculature. When PPH occurs in spite of these preventive measures, therapeutic options include additional uterotonics (medical), uterine tamponade (mechanical) and surgical interventions (vascular ligation, uterine compression sutures and hysterectomy).

Uterine balloon tamponade is often the second line therapy when medical management is unsuccessful and is achieved with inflatable devices inserted into the uterus to exert outward compression on the uterine walls. Despite its widespread use, its mechanism is counterintuitive to the physiologic uterine contraction that occurs after delivery to control bleeding. Its use is further limited by prolonged treatment times (typically 12-24 hours), urinary tract occlusion, and inability to reveal any continuing bleeding. Low-cost options most commonly condom catheters are used in LMICs, but two recent randomized trials showed no improvement in maternal outcomes and possible harm. Thus, there is an urgent need for effective and safe treatment options to reduce the burden of PPH particularly in LMICs.

The Jada® System (Alydia Health, Menlo Park, CA, USA) is a novel U.S. FDA-cleared intrauterine vacuum-induced hemorrhage-control device specifically designed for rapid treatment of PPH. It mimics postpartum physiology by applying low-level intrauterine negative pressure to facilitate uterine compressive forces for constriction of blood vessels to achieve hemostasis. Preliminary data from two studies have shown promising results. The device was first evaluated in a feasibility case series (n=10) in Indonesia and showed rapid treatment of abnormal postpartum uterine bleeding.6 The second larger study, a multicenter single-arm trial (n=106) in the United States, confirmed quick and definitive control of bleeding in 94% of cases within a median time of 3 minutes and few adverse events. While promising, these data are limited by lack of control groups, possible selection bias and the modest sample sizes which preclude definitive conclusions regarding the relative effectiveness and safety of the Jada® System.

We propose the first, definitive, randomized control trial (N=424) to test the hypothesis that the Jada® System is effective, safe and cost-effective in treating PPH, compared to standard care. A multidisciplinary team of investigators with expertise in obstetrics, global health and clinical trials will enroll 424 women in two high volume obstetric units in Ghana, a LMIC with high PPH burden, to pursue the following specific aims:

Primary Aim: Evaluate the effectiveness of the Jada® System, compared to standard care, in treating PPH.

Secondary Aim 1: Assess the safety of the Jada® System, compared to standard care, in treating PPH.

Secondary Aim 2: Estimate the cost-effectiveness of the Jada® System, compared to standard care, in treating PPH.

Eligibility criteria: Inclusion Criteria:

* 18 years or older
* Delivery at 34 weeks or greater
* Cumulative blood loss \>1000ml within 24 hours after delivery
* Uterine atony
* Receipt of first-line uterotonics
* Cervix at least 3cm dilated at cesarean section

Exclusion Criteria:

* Patient unwilling or unable to provide informed consent
* Retained placenta or other known cause of postpartum hemorrhage
* Placenta accreta spectrum
* Coagulopathy
* Rupture uterus
* Surgical management immediately needed for life-threatening bleeding
* Known contraindication for Jada System; ongoing intrauterin pregnancy, untreated uterine rupture, unresolved uterine inversion, current cervical cancer, unknown uterine anomoly, current purulent infection

Primary outcomes:
measure: Maternal survival without surgical intervention
timeFrame: Delivery to 6 weeks post-delivery
Secondary outcomes:
measure: Time from randomization to control of bleeding
timeFrame: 6 weeks postpartum
measure: Concentration of postpartum hemoglobin
timeFrame: Postpartum day 1
measure: Change in hemoglobin concentration from labor admission to postpartum day 1
timeFrame: Postpartum day 1
measure: Rate of maternal transfusion of blood or blood products postpartum
timeFrame: 6 weeks postpartum
measure: Number of units of blood products transfused
timeFrame: 6 weeks postpartum
measure: Volume of blood loss post-randomization
timeFrame: 6 weeks postpartum
measure: Surgical procedures performed
timeFrame: 6 weeks postpartum
measure: Rate of maternal death postpartum
timeFrame: 6 weeks postpartum
measure: Number of additional uterotonic used after randomization
timeFrame: 6 weeks postpartum
measure: Patient satisfaction assessed by a score on a scale of 0 (least satisfied) to 10 (most satisfied)
timeFrame: 6 weeks postpartum
measure: Composite adverse events potentially related to the Jada system
timeFrame: 6 weeks postpartum
measure: Quality-adjusted Life-year
timeFrame: 6 weeks postpartum
measure: Incremental cost per quality-adjusted life-year
timeFrame: 6 weeks postpartum
Other outcomes:
Locations:
city: Kumasi
country: Ghana
facility: Komfo Anokye Teaching Hospital
state: Ashanti Region
city: Accra
country: Ghana
facility: Korle-bu Teaching Hospital
state: Greater Accra Region
Study officials:
affiliation: Women and Infants Hospital of Rhode Island
name: Methodius Tuuli, MD, MPH, MBA
role: PRINCIPAL_INVESTIGATOR
References: