Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202204852865149 Date of Approval: 04/04/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Novel Vacuum-Induced Hemorrhage Control for Postpartum Hemorrhage: a Multicenter Randomized Trial
Official scientific title Novel Vacuum-Induced Hemorrhage Control for Postpartum Hemorrhage: a Multicenter Randomized Trial
Brief summary describing the background and objectives of the trial BACKGROUND: Every year, 130 million women deliver babies around the world, and an estimated 14 million experience postpartum hemorrhage (PPH). It is the leading cause of maternal mortality worldwide, responsible for 25% of maternal deaths from obstetric causes. Although PPH has multiple causes, the most common is uterine atony. Active management of the third stage of labor reduces the incidence of PPH by approximately 66%. When PPH occurs in spite of these preventive measures, therapeutic options include additional uterotonics, uterine tamponade, and surgical interventions. Uterine balloon tamponade is often the second-line therapy, but despite its widespread use, its mechanism is counterintuitive to postpartum uterine physiology. Low-cost options are used in LMICs, but two recent randomized trials showed no benefit and possible harm. Thus, there is an urgent need for treatment options to reduce the burden of PPH particularly in LMICs. The Jada® System is a novel U.S. FDA-cleared intrauterine vacuum-induced hemorrhage-control device 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 are promising, but they are limited by lack of control groups, possible selection bias and the modest sample sizes. OBJECTIVES: This is 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. Primary Objective: Evaluate the effectiveness of the Jada® System, compared to standard care, in treating PPH Secondary Objective 1: Assess the safety of the Jada® System, compared to standard care, in treating PPH Secondary Objective 2: Estimate the cost-effectiveness of the Jada® System, compared to standard care, in treating PPH.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) NOVIC Trial
Disease(s) or condition(s) being studied Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Devices
Anticipated trial start date 01/06/2022
Actual trial start date
Anticipated date of last follow up 31/05/2027
Actual Last follow-up date
Anticipated target sample size (number of participants) 424
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Standard care Once From randomization until bleeding is controlled Patients in this group will receive care according to the treatment algorithm for postpartum hemorrhage from uterine atony at the two teaching hospitals in Ghana. Possible interventions include additional uterotonics, tranexamic acid, and catheter balloon uterine tamponade. If bleeding is uncontrolled, patients will have surgical intervention with options of uterine vascular ligation, uterine compression sutures or hysterectomy. 212 Active-Treatment of Control Group
Experimental Group Jada System Once From insertion until removal, usually one and a half hours after bleeding is controlled Patients in this group will have the Jada® System inserted when the initial medical treatment fails and estimated blood loss reaches 1000 mL. It is a U.S. FDA-cleared novel vacuum induced hemorrhage control device intended for the treatment of postpartum hemorrhage when conservative management is warranted. The device is made of medical-grade silicone. The distal end, which is placed in the uterus, is an elliptical loop. The loop’s inner surface contains 20 vacuum pores protected by a shield that facilitates the creation of a vacuum within the uterine cavity. The loop is soft and smooth to limit the chance of tissue damage during insertion, treatment, and removal of the device. The proximal end has a vacuum connector. The vacuum source is a regulated hospital-grade wall suction or a portable vacuum source with a canister. Prior to placing the device, a manual sweep is performed to ensure that there is no retained placental tissue or clot. The loop of the Jada® System is then inserted into the uterine cavity, and the circular cervical seal, just outside the external cervical os, is filled with 60 – 120 mL sterile water. A low-level vacuum (80 ± 10 mm Hg) is applied and pooled blood is evacuated from the uterus as it collapses. The volume of any ongoing bleeding is measured in the suction tubing and canister while the uterine response to treatment can be palpated. Once there is no bleeding, the device remains in the uterus for at least 1 hour. The suction is then disconnected, the seal emptied of water, the device left in place, and the patient monitored for an additional 30 minutes. If bleeding remains controlled, the device is removed. If bleeding is uncontrolled with the Jada® System patients will have a surgical intervention with options of uterine vascular ligation, uterine compression sutures or hysterectomy. 212
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. 18 years or older 2. Delivery at 34 weeks or greater 3. Vaginal or cesarean delivery 4. Cumulative blood loss>1000ml within 24 after delivery 5. Uterine atony 6. Receipt of first-line uterotonics 7. Cervix at least 3 cm dilated at cesarean section 1. Patient unwilling or unable to provide informed consent 2. Retained placenta or other known cause of postpartum hemorrhage 3. Placenta accreta spectrum 4. Coagulopathy 5. ruptured uterus 6. Surgical management immediately needed for life-threatening bleeding 7. Known contraindication for Jada System: on-going intrauterine pregnancy, untreated uterine rupture, unresolved uterine inversion, current cervical cancer, unknown uterine anomaly, current purulent infection. Adult: 19 Year-44 Year 18 Year(s) 45 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 17/03/2022 Korle bu Teaching Hospital Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
Guggisberg Avenue Accra P.O. 4236 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Maternal survival without surgical intervention. 6 weeks post-delivery
Secondary Outcome Time from randomization to control of bleeding 6 weeks postpartum
Secondary Outcome Postpartum hemoglobin Postpartum day 1
Secondary Outcome Change in hemoglobin from labor admission to postpartum day 1 Postpartum day 1
Secondary Outcome Maternal transfusion of blood or blood products postpartum 6 weeks postpartum
Secondary Outcome Number of units of blood products transfused 6 weeks postpartum
Secondary Outcome Estimated blood loss post-randomization 6 weeks postpartum
Secondary Outcome Surgical procedures performed, including uterine vascular ligation, uterine compression sutures and hysterectomy. 6 weeks postpartum
Secondary Outcome Maternal death postpartum 6 weeks postpartum
Secondary Outcome Additional uterotonic used after randomization 6 weeks postpartum
Secondary Outcome Patient satisfaction score on a scale of 0 (least satisfied) to 10 (most satisfied) 6 weeks postpartum
Secondary Outcome Composite adverse events potentially related to the Jada System, including genital tract injury, uterine perforation or rupture and endometritis. 6 weeks postpartum
Secondary Outcome Quality-adjusted Life-year based on the literature and Quality of Life Questionnaire (EQ-5D-5L) 6 weeks postpartum
Secondary Outcome Incremental cost per quality-adjusted life-year 6 weeks postpartum
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Korle Bu Teaching hospital Guggisberg Avenue, Accra Accra Ghana
Komfo Anokye Teaching Hospital Komfo Anokye Road, Kumasi Kumasi Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institute of Child and Human Development Bldg 31, Room 2A32, MSC 2425 31 Center Drive Bethesda MD 2089 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Women and Infants Hospital of Rhode Island Warren Alpert Medical School at Brown University 101 Dudley Street Providence R1 02905 United States of America Hospital
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Methodius Tuuli mtuuli@wihri.org +16785582874 101 Dudley Street
City Postal code Country Position/Affiliation
Providence RI 02905 United States of America Professor and Chair Department of Obstetrics and Gynecology Warren Alpert School of Medicine at Brown University
Role Name Email Phone Street address
Scientific Enquiries Samuel Oppong saoppong@ug.edu.gh +233206301387 26 Slater Av, Korlebu, Accra
City Postal code Country Position/Affiliation
Accra Ghana Senior Lecturer and Head Department of Obstetrics and Gynaecology University of Ghana Medical School
Role Name Email Phone Street address
Public Enquiries Methodius Tuuli mtuuli@wihri.org +16785582874 101 Dudley Street
City Postal code Country Position/Affiliation
Providence RI 02818 United States of America Professor and Chair Women and Infants Hospital of Rhode Island
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data will be collected from human subjects and will be shared according to NIH guidelines. We are committed to the sharing of final data, being mindful that the rights and privacy of people who participate in research must be protected at all times. We will make a complete study dataset available for sharing. We will have a description of study dataset, including code books, meta-data related to the dataset, and documented programming code used for creating the final study population, for creating variables, and for conducting all outcomes analyses. We will remain HIPAA compliant, and therefore any datasets resulting from participants will be free of any identifiers that would permit linkages to individual research participants and variables that could lead to deductive disclosure of individual subjects. Even then, there remains the possibility of deductive disclosure of subjects with unusual characteristics. Data may be distributed by a number of electronic methods, including web-based databases, datasets, and spreadsheets, or via electronic media such as compact discs. Statistical Analysis Plan,Study Protocol 24 months after publication of primary manuscript. We will make the data and associated documentation available to users under a data-sharing agreement that provides for commitment to: a) using the data only for research purposes and not to identify any individual participant; b) securing the data using appropriate computer technology; and c) destroying or returning the data after analyses are completed. Timelines for distribution of data will vary depending on any required restrictions as mentioned above.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information