Postpartum Hemorrhage (PPH) is an obstetric emergency that can occur up to 24 hours after vaginal birth or cesarean section and the main cause for maternal death. PPH is mainly caused by uterine atony and is involved in 75% of primary PPH. The intention of the Alma system clinical study is to prevent PPH, when manual contraction and first-line conservative therapies have failed, treatment that quickly and effectively reduces or stops blood flow by addressing the driving cause of hemorrhage: uterine atony.

This will be a prospective, non-randomized, feasibility pilot study of 10 women with vaginal deliveries in a hospital setting who failed first-line therapies for postpartum hemorrhage. It is expected to take approximately 12 months to enroll, treat, and follow up on all 10 subjects.

The primary objective is to verify the safety of the Alma Device in humans, including:

1. Absence of Serious Adverse Events (SAEs) related to the use of the Alma System intra- and post-procedure.
2. Evaluate any observable damage to the uterus, cervix, or vagina due to the use of the Alma System.
3. Evaluate the occurrence of uterine inversion or folding during the use of the Alma System.

The primary outcomes include,

1. Rate of device related SAE up to six weeks following device treatment.
2. Rate of any observable damage to cervix, uterus or vagina during or immediately after device procedure.
3. Rate of occurrence of uterine inversion of folding during or immediately after device procedure. There will be no formal statistical rule for stopping the study has been defined due to the observational nature of the study.

Background: Postpartum Hemorrhage (PPH) is commonly defined as a blood loss of 500 ml or more within 24 hours after birth, while severe PPH is defined as a blood loss of 1000 ml or more within the same timeframe. PPH affects approximately 2% of all women who give birth: it is associated not only with nearly one quarter of all maternal deaths globally but is also the leading cause of maternal mortality in most low-income countries. PPH is a significant contributor to severe maternal morbidity and long-term disability as well as to a number of other severe maternal conditions generally associated with more substantial blood loss, including shock and organ dysfunction. Treatment for primary PPH requires a multidisciplinary approach. The WHO guideline for the Active Management of the Third Stage of Labor (AMTSL) is recommended for all patients in order to prevent PPH. 

Main Objective:

To determine the efficacy and duration of action of the Alma system to arrest Postpartum Hemorrhage.

2. Specific Objectives:

Primary objectives:

The primary objectives is to verify the safety of the Alma System, including:

1. Absence of Serious Adverse Events (SAEs) related to the use of the Alma System intra- and post-procedure.
2. Evaluate any observable damage to the uterus, cervix, and vagina due to the use of the Alma System.
3. Evaluate occurrence of uterine inversion or folding during the use of the Alma System.

Secondary Objectives:

The secondary objectives include evaluations of:

1. Ability to easily place the Alma System transvaginally.
2. Ability to connect the Alma System to vacuum and maintain desired negative pressure.
3. Ability of Alma System to contract the uterus to a level that reduces or stops blood loss and avoids further non-surgical and surgical intervention.
4. Evaluate time from insertion and start negative pressure to visible reduction of blood loss.

Methods - A multicenter, prospective, single-arm treatment study of a novel intrauterine device that uses low-level vacuum to induce uterine myometrial contraction to achieve control of abnormal postpartum uterine bleeding and postpartum hemorrhage was undertaken at 12 centers in the United States. The primary effectiveness endpoint was the proportion of participants in whom use of the intrauterine vacuum-induced hemorrhage-control device controlled abnormal bleeding without requiring escalating interventions. The primary safety endpoint was the incidence, severity, and seriousness of device-related adverse events. Secondary outcomes included time to bleeding control, rate of transfusion, and device usability scored by each investigator using the device.

Study population - Ten (10) Women with vaginal deliveries in a hospital setting who failed first-line therapies for postpartum hemorrhage. Study subjects will be recruited by the PI from among his/her hospital patients. Patients who may be eligible for enrollment will be approached, have the study explained to them in full, and will be provided with the ICF.

Inclusion criteria

1. Adult Female, 18 years of age or older at time of consent.
2. Subject or her legally authorized representative is able to understand and provide consent to participate in the clinical investigation
3. Subjects who present with an atonic uterus for at least 10 minutes after expulsion of placement with failure to obtain contraction and/or Subjects who have lost blood post-partum >= 500 ml and according to the Investigator's judgment, require an intervention.
4. Failed first-line intervention of uterotonics and uterine massage/bimanual uterine massage to stop bleeding.

Exclusion  criteria

1. Subjects who do not provide informed consent to participate in the clinical investigation.
2. Subjects who deliver at a uterus size < 34 weeks.
3. Subjects who have lost greater than 1000 ml of blood.
4. Subjects who have abnormal PT, PTT and INR
5. Subjects who present with retained placenta, uterine lacerations, or for any other conditions outside of atonic post-partum hemorrhage.

Data Management and Statistical Analysis: Monitoring functions shall be performed in compliance with Good Clinical Practice per ISO 14155:2020, and as outlined in 21CFR§821.43(d) and 21CFR§812.46.

A Case Report Form (CRF) booklet for each subject enrolled in the study will be used. CRFs must be fully completed for each subject and signed by the investigator in blue or black ink and monitored as per standard requirement. The sponsor will train the site personnel to correctly record the clinical data into the CRF. Each study follow-up will be completed and signed by the investigator in blue or black ink. Any corrections will be made by drawing a single line through the incorrect entry, entering the correct information, and initialing and dating the change. Data entry boxes or spaces should not be left blank, but instead should indicate: NA for not applicable, ND for not done or “-“for missing or not available data.  All CRFs will be tracked and missing or unclear data will be requested as necessary through the trial. The originally signed CRFs will be delivered to the sponsor after source verification.

Statistical considerations: Up to 10 patients will be enrolled. No formal statistical rule for stopping the study has been defined due to the observational nature of the study.

Significance: The intention of the Alma system clinical study is to provide women with PPH, when first-line conservative therapies have failed, treatment that quickly and effectively reduces or stops blood flow by addressing the driving cause of hemorrhage: uterine atony.