None listed
Conditions
Brief summary
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 21 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, the woman will be approached for participation in the trial if she is in early labour and if her vital signs are normal, and she is not distressed. 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 for the first 60 minutes. 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 oxytocin arm (active control) will receive 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 calibrated 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 a minimum of 24 hours after randomization or until hospital discharge, or transfer to higher-level care, 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.
Interventions
The IMP for the trial will be: a once-off Intravenous infusion following PPH diagnosis of Heat Stable Carbetocin (HSC) 100 µg in 100 ml normal saline administered over 5 min, followed by a once-off infusion of 500 ml normal saline over 4 hours.
This will be documented directly within worksheets within the patient medical records.
Sponsors
WHO
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants will be eligible for randomization if they fulfil all the following criteria: • had a singleton pregnancy • had a vaginal birth • receive HSC for PPH prophylaxis during the vaginal birth • have an indication to receive uterotonics for the first response treatment of PPH presumably due to uterine atony (clinically diagnosed, or measured blood loss of 500 ml or more from the vagina, and where known coagulopathy and retained placenta has been excluded as the cause of bleeding) • provided written informed consent before any trial-related procedures are carried out.
Exclusion criteria
Participants will be excluded from participating in the trial if they have any of the following criteria: • known history of allergy to HSC or oxytocin or excipients in the medicinal products used in the trial • known serious coagulopathy, epilepsy, hepatic, renal, or cardiovascular disease • known intrauterine fetal death • birth that is considered an abortion according to local gestational age limit • other clinically significant condition(s) that, in the opinion of the investigator could represent increased health risk for the participation of the woman or interfere with the objectives of the trial • a manual removal of placenta • a placenta in-situ that has not been expelled or removed • known administration of any uterotonic for PPH treatment (e.g. prostaglandins, oxytocin, ergometrine) following PPH prophylaxis.
Outcome results
None listed