Jada Mechanism of Action

Pharmacology: Pharmacodynamics: Summary of Clinical Data: The safety and effectiveness of the Jada System was evaluated in the PEARLE study (Prospective, Single Arm, Pivotal Clinical Trial Designed to Assess the Safety and Effectiveness of the Jada System In Treating Primary Postpartum Hemorrhage "PPH") under an approved IDE from the U.S. Food and Drug Administration (FDA).
Study Design: PEARLE was a prospective, single-arm, literature-controlled, multi-center treatment study where each enrolled subject was treated with the Jada System. The primary endpoints of the study were: Primary Effectiveness Endpoint: control of postpartum hemorrhage, defined as the avoidance of non-surgical, second line or surgical intervention to control uterine hemorrhage after the use of the Jada System per the Instructions for Use under Dosage & Administration.
Primary Safety Endpoint: incidence, severity and seriousness of adverse events related to Jada.
The following Secondary Endpoints were evaluated in the PEARLE study: Time to hemorrhage control.
Rate of non-surgical intervention required to control PPH after Jada use.
Rate of surgical intervention required to control PPH after Jada use.
Assessment of device usability.
Rate of blood product transfusion required after Jada use, and number of transfusion units when administered.
Use of the Jada System occurred after failure of first line uterotonics and uterine massage.
The comparator to the Jada System was a literature meta-analysis of the Bakri Postpartum Balloon. Based on a random effects model used in the meta-analysis, the estimated pooled proportion of subjects who reached control of uterine hemorrhage following Bakri Postpartum Balloon treatments was 82.0% (95% CI: 73.4% to 89.2%). By this definition, the study was considered a success if the lower bound of the two-sided Exact Clopper-Pearson mid-p 95% Confidence Interval for the Study Treatment Success was greater than or equal to 73.4%.
A total of 107 subjects were enrolled in PEARLE at 12 investigational centers in the United States. (See Table 1.)

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Primary Endpoints: Effectiveness: The analysis of effectiveness was based on the 106 subjects in the ITT Cohort. Results from the 104 subjects in the mITT and 97 subjects in the PP Cohort are also presented. The treatment success rate in the ITT Cohort was 94.3% (100/106, p<0.001), with a lower bound 95% confidence limit of 88.1%. One subject counted as a success in the study was treated with uterine balloon tamponade (UBT) prior to meeting the minimum EBL threshold. The UBT treatment was unsuccessful and continued blood loss occurred. After meeting the EBL threshold, the subject was treated with Jada which controlled hemorrhage without requiring further treatment. The treatment success rate of the comparator, the Bakri Postpartum Balloon, was 82.0% (95% CI: 73.4% to 89.2%). The treatment success rate in the mITT Cohort was 96.2 (95% CI: 90.4%, 98.9%). The confidence intervals for the mITT cohort and the meta-analysis of the comparator do not overlap. (See Table 2 and figure.)

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Safety: The analysis of safety was based on the 106 subjects in the Safety/ITT Cohort. There were no adverse events judged definitely related to the device or the procedure and there was a low rate of possibly related adverse events, all of which were anticipated in this patient population and with introduction of an intrauterine device. Five possibly device-related adverse events were rated as "mild" and three were rated as "moderate" without any event in this group rated "severe". The three moderate events were cases of endometritis, which is a known risk of long labor, vaginal exam, and PPH.
Secondary Endpoints: Control of hemorrhage was defined in the protocol as the time from connecting the vacuum source to Jada to the time the first of any of the following occurs: there is no blood being collected in the tubing or canister, or the blood loss is observed as leveled off in the canister, or blood loss is at a rate of <500 mL in 24 hours. The median time to control of PPH in the ITT, mITT and PP population was 3 minutes.
Timing of the procedure and duration of treatment was tracked from diagnosis through treatment and patient discharge for subjects enrolled in PEARLE. Jada was used most often within one hour after delivery. Bleeding was controlled quickly from the time of connection of vacuum, with a median control in three minutes. The duration of treatment with active vacuum connected was a median of 2 hours and 24 minutes with total in-dwelling time median of 3 hours and 11 minutes. (See Table 3.)

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The median hospital length of stay from delivery time was 2.2 days.
The need for non-surgical intervention after use of Jada was rare, with only 2 subjects receiving non-surgical intervention in the ITT Cohort.
Surgical intervention after Jada treatment was reported in three subjects: one subject received a B-Lynch compression suture in conjunction with Jada, one subject received B-Lynch compression suture followed by hysterectomy, and one subject underwent hysterectomy. (See Table 4.)

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The device usability was notably positive by investigators on all measurements. (See Table 5.)

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Additional Treatment: A subset of subjects received tranexamic acid (TXA) along with uterotonics and uterine massage for treatment of PPH. TXA was used in 41/106 (39%) subjects in the ITT cohort. (See Table 6.)

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The safety data evaluation showed there were no device deficiencies or adverse events reported related to use of TXA in study subjects. (See Table 7.)

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Additional Analyses by Delivery Mode: Sub-group analysis of effectiveness rate was evaluated by mode of delivery, vaginal or c-section. For the ITT population of 106 subjects, there were 91 vaginal deliveries with three failures, and 15 c-sections with three failures. One subject counted as a success in the study was treated after vaginal delivery with uterine balloon tamponade (UBT) prior to meeting the minimum EBL threshold. The UBT treatment was unsuccessful and continued blood loss occurred. After meeting the EBL threshold, the subject was treated with Jada which controlled hemorrhage without requiring further treatment. The success rates in the ITT Cohort were 96.7% and 80.0% after vaginal and c-section birth, respectively. In the mITT Cohort, success rates were 98.9% and 80.0%, respectively. In the PP Cohort, the success rates were 100.0% and 91.7%, respectively. (See Table 8.)

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Summary: The results of the PEARLE study demonstrated that the Jada System is safe with an effectiveness rate of 94.3% for its intended use. The effectiveness rates in the mITT and PP Cohorts were 96.2% and 99.0%, respectively. There were no adverse events judged definitely related to the device or the procedure, and there was a low rate of possibly related adverse events, all of which were anticipated in this patient population and with introduction of an intrauterine device.
The secondary endpoints were also overwhelmingly positive. Bleeding was controlled in 3 minutes in the ITT, mITT and PP populations. The rate of further surgical or non-surgical intervention after Jada was very low. The rate of blood transfusion was expected in this patient population, treated at U.S. hospitals with ready access to these resources. The median reported total time for Jada treatment with vacuum in this study was 2 hours and 24 minutes, and total in-dwelling time was 3 hours and 11 minutes.
Additional clinical data collected outside the United States: First-in-Woman Study Results: A First-in-Woman (FIW) feasibility study with Ethics Committee oversight was conducted at two clinical sites in Indonesia. The purpose of the study was to demonstrate the placement, function, and operation of the Jada System to meet its intended use.
Ten subjects were enrolled in the feasibility study. None of the subjects presented with a retained placenta, uterine lacerations, uterine scarring, or for any conditions other than atonic postpartum hemorrhage. Bleeding was controlled within two minutes for all ten subjects. Evaluation of the primary clinical data safety endpoints determined that: 1) no safety issues were observed relative to the placement, insertion, or removal of the Jada, 2) there were no complications related to delayed arrest of blood loss, 3) there was no damage to the uterus, cervix, or vagina, and 4) no uterine inversion or folding events were observed during the Jada procedure.
Case Series Outside the United States: Thirteen subjects were enrolled at the clinical trial site at St. Francis Hospital Nsambya, in Kampala, Uganda under an earlier iteration of the PEARLE study protocol with similar inclusion/exclusion criteria.
Jada was effective at treating PPH in all 13 subjects, including three subjects who were enrolled despite estimated blood loss (EBL) at study entry significantly higher than allowed per study inclusion criterion. Hemorrhage was controlled in each subject but two subjects subsequently died due to lack of blood product supply for transfusion to treat their severe blood loss. There were no adverse events designated definitely related to the device or the procedure.