Title: A Phase III Trial Comparing HSC and Oxytocin for Postpartum Hemorrhage Prevention

Objective: This international, multicenter trial aims to compare the effectiveness and safety of intravenous HSC (an investigational uterotonic) with oxytocin (the current standard) for preventing postpartum hemorrhage (PPH).

Study Design:

Type: Hospital-based, parallel, two-arm, individually-randomized, double-blind, active controlled.

Participants: Pregnant women at 20 tertiary level hospitals across Argentina, Kenya, India, Nigeria, Uganda, South Africa, and the United Kingdom.

Eligibility: Women in early labor with normal vital signs and no distress.

Randomization: Participants will receive either HSC or oxytocin as the first-line uterotonic.

Treatment Administration: Women having a vaginal birth will receive an intramuscular prophylactic dose of HSC. If atonic PPH occurs (500 ml blood loss or more), they will be randomized to receive either HSC or oxytocin via intravenous infusion.

Follow-up: All women will be monitored for 24 hours after randomization or until hospital discharge.

Safety Sub-Study:

An internal safety sub-study will assess the comparative safety of HSC versus oxytocin.

The first interim analysis will occur after enrolling the first 250 participants.

This trial aims to improve PPH management and enhance maternal health outcomes.

This will be a phase III, hospital-based, parallel, two-arm, individually-randomized, double-blind, active controlled, international, multicentre, non-inferiority trial. Participating women will be randomized to receive either intravenous HSC or oxytocin as the ‘first-line’ uterotonic for PPH treatment.

The trial will be conducted across 20 tertiary level hospitals within the WHO “CHAMPION” Trial Network in Argentina, Kenya, India, Nigeria, Uganda, South Africa, and United Kingdom.

Care providers will inform potentially eligible pregnant women about the trial during their antenatal care visits to the hospital. If a woman is seen for the first time during her admission to the hospital for childbirth, she will be provided information about the trial then. Women will be approached for participation in the trial if she is in early labour (<6cm cervical dilatation), her vital signs are normal, and she is not distressed at the moment of giving consent. Informed consent will be obtained from the woman before any trial-related procedures are carried out.

Women having a vaginal birth who have been consented in early labour will receive an intramuscular (IM) prophylactic 100 µg dose of HSC for PPH prevention. Following the birth of the baby, a calibrated drape will be placed under the woman’s buttocks to measure blood loss following birth. Should atonic PPH based on a clinical diagnosis or blood loss estimation of 500 ml or more occur, the woman will be randomized to receive a saline intravenous (IV) infusion of HSC 100 µg or oxytocin 5 IU over 5 minutes. Following this treatment, women in the oxytocin arm (active control) will receive an additional 20 IU at a lower saline infusion rate over 4 hours in line with standard clinical practice, while women in HSC arm will receive an equivalent amount of saline infusion but with no additional uterotonic for the same period. Upon randomization, a new drape will be placed under the woman’s buttocks to measure further blood loss for 90 minutes. 

The investigational medicinal product (IMP) will be administered immediately following randomization of trial participants. Once the IMP has been administered to the woman as described above, the clinical staff will continue further PPH management in accordance with existing hospital PPH management protocol and WHO guidelines.

All women will be followed up for 24 hours after randomization or until hospital discharge, whichever is soonest.

The trial will be implemented with an internal safety sub-study. The first interim analysis will be conducted for an independent Data Safety Monitoring Committee (DSMC) to assess comparative safety of HSC versus oxytocin once the first 250 participants have been enrolled into the trial.