Heat-stable carbetocin for the treatment of postpartum haemorrhage: a phase III, randomized, double-blind, active controlled, multicountry, multicentre, non-inferiority trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6,200
- 试验地点
- 6
- 主要终点
- To evaluate whether heat-stable carbetocin (HSC) is non-inferior to oxytocin for treatment of postpartum haemorrhage (PPH) in women who receive HSC for PPH prophylaxis, in the prevention of additional blood loss of 500 ml or more
研究概览
简要总结
This is a phase III, randomised, double-blind, multicentre, international trial aiming to evaluate the efficacy and safety of heat-stable carbetocin (HSC) for treatment of postpartum haemorrhage (PPH) in women who have had a vaginal birth.
6,200 participating women with vaginal births who have received HSC as prevention for PPH, will be randomised to receive either intravenous HSC or oxytocin as the ‘first-line’ PPH treatment. Once administered, 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 randomisation or until hospital discharge, whichever is soonest.
The trial will be conducted across 20 tertiary level hospitals within Argentina, Kenya, India, Nigeria, Uganda, South Africa, and United Kingdom. Recruitment for the trial will occur over 30 months.
An initial, internal, comparative safety sub-study is embedded in this trial to robustly evaluate the comparative effects of HSC versus oxytocin on specific haemodynamic outcomes. The safety sub-study will enroll 250 women and will be conducted in selected hospitals in Argentina, South Africa and United Kingdom. An independent Data Safety Monitoring Committee (DSMC) will examine the results from the interim analysis of this safety sub-study and make recommendations on whether to progress to full-scale trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 50.00 Year(s)（—）
- 性别
- Female
入选标准
- •Trial participants will be postpartum women with a clinical or volumetric diagnosis of PPH after a vaginal birth.
- •Trial participants must have received a prophylactic intramuscular (IM) dose of HSC for PPH prevention.
- •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.
排除标准
- •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.
结局指标
主要结局
To evaluate whether heat-stable carbetocin (HSC) is non-inferior to oxytocin for treatment of postpartum haemorrhage (PPH) in women who receive HSC for PPH prophylaxis, in the prevention of additional blood loss of 500 ml or more
时间窗: Proportion of women with additional vaginal blood loss of more than or equal to 500 ml at 90 minutes following randomisation
次要结局
- Additional blood loss of more than or equal to 1000 ml(At 90 minutes following randomisation)
- Use of additional uterotonic(s)(At 90 minutes following randomisation)
- Additional blood loss of more than or equal to 500 ml OR use of additional uterotonic(s)(At 90 minutes following randomisation)
- Use of surgical procedure(s) related to PPH (uterine balloon tamponade, laparotomy for either compressive sutures, artery ligation or hysterectomy)(As at 24 hours following randomisation)
- Occurrence of clinically significant cardiac arrhythmia based on clinical judgement which requires treatment(Up to 24 hours)
- Amount of blood loss(At 90 minutes following randomisation)
- Use of additional uterotonics(As at 24 hours following randomisation)
- Use of blood transfusion products(As at 24 hours following randomisation)
- Admission to intensive care unit(As at 24 hours following randomisation)
- Maternal death(As at 24 hours following randomisation)
- Clinically defined coagulopathy(As at 24 hours following randomisation)
- Breastfeeding(As at 24 hours following randomisation)
- Occurrence of shock(Up to at 24 hours following randomisation)
- Frequency and severity of adverse or serious adverse events(As at 24 hours following randomisation)
- Composite outcome of maternal death or severe morbidity(As at 24 hours following randomisation)
- Any haemodynamic change requiring therapeutic intervention(During the 10 minutes of initiating treatment infusion)
- Occurrence of clinically significant cardiac arrhythmia based on clinical judgement(Requiring treatment in the first 10 minutes after initiating treatment infusion)
- Occurrence of clinically significant cardiac arrhythmia based on clinical judgement which results in cardiac arrest(During the first 24 hours following randomisation)
研究者
Dr Shivaprasad S Goudar
KLE Academy of Higher Education and Researchs J N Medical College