E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Mother Bleeding after Birth |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10005128 |
E.1.2 | Term | Bleeding postpartum |
E.1.2 | System Organ Class | 100000004868 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
-To evaluate non-inferiority of carbetocin RTS 100 µg IM versus oxytocin 10 IU IM after vaginal delivery in the prevention of the composite endpoint “blood loss of 500 mL or more or the use of additional uterotonics” at one hour and up to two hours for women who continue to bleed after one hour.
-To evaluate non-inferiority of carbetocin RTS 100 µg IM versus oxytocin 10 IU IM in the prevention of sPPH (≥1000 mL blood loss) at one hour and up to two hours for women who continue to bleed after one hour. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants will be eligible for the trial if:
1. They are expected to deliver vaginally
2. They have a cervical dilatation equal to or less than 6cm
3. They have a known singleton pregnancy
4. They provide written informed consent before any trial-related procedures are carried out.
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E.4 | Principal exclusion criteria |
Participants will be excluded from participating in the trial if they are/have:
1. In an advanced first stage of labour (>6 cm cervical dilatation) or too distressed to understand, confirm and give informed consent regardless of cervical dilatation
2. Non-emancipated minors (as per local regulations) without a guardian
3. Scheduled for a planned caesarean section
4. A birth considered as an abortion according to local guidelines
5. Known allergies to carbetocin, other oxytocin homologues or excipients in the medicinal products used in the trial
6. Serious cardiovascular disorders
7. Not capable of giving consent due to other health problems such as obstetric emergencies (e.g. antepartum haemorrhage) or mental disorder.
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E.5 End points |
E.5.1 | Primary end point(s) |
- The proportion of women with blood loss of 500 mL or more or the use of additional uterotonics at one hour and up to two hours for women who continue to bleed after one hour.
- The proportion of women with blood loss of 1000 mL or more at one hour and up to two hours for women who continue to bleed after one hour.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
for both end points: 60 minutes after delivery or 120 minutes for women who continue to bleed
after one hour. |
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E.5.2 | Secondary end point(s) |
1 The proportion of women with blood loss of 500 mL or more at one hour (or two hours postpartum if the bleeding continues beyond one hour).
2 Blood loss in mL at one hour (or two hours postpartum if the bleeding continues beyond one hour).
3 The proportion of women receiving additional uterotonics at one hour (or two hours postpartum if the bleeding continues beyond one hour).
4 The proportion of women receiving additional uterotonics up to time of discharge.
5 The proportion of women receiving blood transfusion up to time of discharge.
6 The proportion of women with manual removal of placenta up to time of discharge.
7 The proportion of women having additional surgical procedures (e.g. suturing of cervix/high vaginal tear, exploration of uterine cavity under general anaesthetic, uterine compression suture, uterine or hypogastric ligation, hysterectomy) up to time of discharge.
8 The proportion of maternal death.
9 The proportion of women with composite outcome of maternal death or severe morbidity (admission to intensive care unit, hysterectomy, blood loss of two liters or more, uterine inversion) up to time of discharge.
10 The incidence and severity of adverse or serious adverse events up to time of discharge.
11 Newborn outcomes (vital status, APGAR score at 5 minutes, resuscitation of the baby, mechanical ventilation).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For end points 1,2,3: One hour (or two hours if the bleeding continues beyond one hour).
For end points 4,5,6,7,8,9,10,11: Hospital discharge |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Egypt |
India |
Kenya |
Nigeria |
Singapore |
South Africa |
Thailand |
Uganda |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For administrative and safety reporting purposes the end of the trial will be defined as the date of the final clinical database lock. This provides for a single and conservative definition across all trial centers. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |