Oxytocin injection and misoprostol tablet compared to oxytocin-ergometrine injection and placebo tablet to prevent bleeding after vaginal delivery
| ISRCTN | ISRCTN44900603 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44900603 |
- Submission date
- 03/01/2025
- Registration date
- 14/01/2025
- Last edited
- 13/01/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
Worldwide, severe bleeding due to childbirth is a primary cause of the death of new mothers accounting for 8 to 20% of the deaths. Severe bleeding can also cause multiple body organs to fail and removal of the womb to control bleeding. The main cause of severe bleeding is the failure of the womb to contract adequately or maintain the contracted state following separation and delivery of the afterbirth. It is standard practice worldwide to routinely give medicines that increase womb contraction immediately at delivery to reduce bleeding. Oxytocin is a natural substance (hormone) released by a part of the brain to quickly and effectively cause womb contraction but it lasts only a short time (minutes) whereas the risk of bleeding if the womb is relaxed persists for many hours. In Malaysia, oxytocin is combined with ergometrine (a slower-acting but longer-lasting medicine to maintain womb contraction) as an injection for a more sustained effect. However, ergometrine can cause side effects like increasing blood pressure which can be of concern as high blood pressure is a common complication during pregnancy. High blood pressure due to pregnancy can show itself for the first time in the hours or days after birth has occurred. Therefore, ergometrine may worsen further the unanticipated high blood pressure that is only revealed after birth.
Misoprostol is a different type of longer-lasting womb contraction-sustaining medicine that can be taken orally. Misoprostol does not appear to cause high blood pressure and likely has a different side effect profile from ergometrine. Both ergometrine and misoprostol are shown to be similarly effective at reducing childbirth-related bleeding in combination with oxytocin. A direct comparative study of oxytocin-misoprostol compared to oxytocin-ergometrine in the context of their use to prevent childbirth-related bleeding based on their side effects and effectiveness in reducing bleeding has not been performed. This study aims to evaluate oxytocin (injection) and misoprostol (tablet) compared to oxytocin-ergometrine (single injection) and placebo (tablet) immediately at vaginal delivery on side effects and blood loss.
Who can participate?
Patients expecting a vaginal delivery, age 18-45 years, term (≥37 weeks of pregnancy), single baby in head down presentation, not more than 4 previous births.
What does the study involve?
Only patients who delivered vaginally will receive the trial medicines as randomly assigned by a computer. Oxytocin injection combined with oral misoprostol tablets or fixed-dose single injection of oxytocin and ergometrine (syntometrine) with oral placebo (non-active) tablets, given one time only at the delivery of the baby and before the placenta is delivered.
What are the possible benefits and risks of participating?
Oxytocin injection combined with oral misoprostol and a fixed dose single injection of combination oxytocin and ergometrine (Syntometrine®) to prevent childbirth-related bleeding has been evaluated in other studies and shown to be effective and reasonably well tolerated. However, these combinations have not been directly compared within a study. Major benefits or differences in bleeding between them are not anticipated. Any benefit or harm is within their side effects profiles. These side effects are anticipated to be mild and short-lasting only. The study will provide high-quality comparative data to guide future care of universally applied medications during childbirth.
Where is the study run from?
Labour ward, Universiti Malaya Medical Centre
When is the study starting and how long is it expected to run for?
January 2024 to October 2026
Who is funding the study?
Department of Obstetrics and Gynaecology, Universiti Malaya Medical Centre
Who is the main contact?
Dr Hemavahthy Mani, hemavahthymani@gmail.com
Contact information
Public, Scientific, Principal Investigator
Medical Officer, Obstetrics and Gynaecology
Pusat Perubatan Universiti Malaya
Lembah Pantai
Kuala Lumpur
59100
Malaysia
| Phone | +60 01126364662 |
|---|---|
| hemavahthymani@gmail.com |
Public, Scientific
Obstetrics and Gynaecology
Pusat Perubatan Universiti Malaya
Lembah Pantai
Kuala Lumpur
59100
Malaysia
| tanpengchiong@yahoo.com |
Public, Scientific
Obstetrics and Gynaecology
Pusat Perubatan Universiti Malaya
Lembah Pantai
Kuala Lumpur
59100
Malaysia
| thaiying.wong@gmail.com |
Study information
| Study design | Participant-blinded parallel-group randomized trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | 46638_PIS_09Jul2024.pdf |
| Scientific title | Intramuscular oxytocin & oral misoprostol versus intramuscular fixed dose oxytocin-ergometrine & oral placebo tablet for postpartum haemorrhage prophylaxis following vaginal delivery: a randomised controlled trial |
| Study acronym | MisO Study |
| Study hypothesis | We hypothesize that oxytocin 10 IU i.m. plus oral misoprostol 600 mcg compared to fixed dose oxytocin 5 IU-ergometrine 500 mcg i.m. plus oral placebo tablet will have different impact on hypertension and fever in the one hour after delivery |
| Ethics approval(s) |
Approved 07/11/2024, Medical Research Ethics Committee of University of Malaya Medical Centre (Lembah Pantai, Kuala Lumpur, 59100, Malaysia; +80 03-79493209/2251; iresearch@ummc.edu.my), ref: 2024117-13252 |
| Condition | Prevention of postpartum haemorrhage, tolerability of prophylactic agents |
| Intervention | Patient recruitment will take place in antenatal or labour ward of UMMC. All women admitted for a planned vaginal birth will be assessed for eligibility. A Patient Information Sheet will be provided. Oral questions about the study will be invited and answered by the recruiting provider. Written informed consent will be taken from all who agree to participate. Participants will be randomised only at vaginal delivery to: i) i.m. oxytocin 10 IU and oral misoprostol 600 mcg tablet OR ii) i.m. syntometrine (fixed dose oxytocin 5 IU and ergometrine 500mcg) plus oral placebo Given at the delivery of the anterior shoulder or latest before delivery of the placenta. These prepared interventions will be placed in the sealed opaque numbered randomization envelopes. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Tolerability |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Oxytocin for injection (10 IU), syntometrine for injection (fixed dose oxytocin 5 IU and ergometrine 0.5 mg), oral misoprostol tablet, placebo tablet |
| Primary outcome measure | One hour after delivery, the presence of: 1. Hypertension (systolic ≥ 140 mmHg and/or diastolic ≥ 90 mmHg) measured using a hospital-grade automated blood pressure device 2. Fever (body temperature ≥ 37.5 0C) measured using a hospital-grade thermometer |
| Secondary outcome measures | 1. Delivery blood loss measured using data collected from participant electronic medical records (EMR) at hospital discharge 2. Use of additional haemostatic intervention (e.g., uterotonics, operative interventions) measured using data collected from EMR at hospital discharge 3. Transfer for a higher level of care (HDU or ICU) measured using data collected from EMR at hospital discharge 4. Blood transfusion measured using data collected from EMR at hospital discharge 5. Women's sense of wellbeing measured using a 0-10 Numerical Rating Scale (NRS) before hospital discharge 6. Satisfaction with the allocated intervention measured using a 0-10 NRS) before hospital discharge 7. Interval to first satisfactory breastfeeding (from maternal perspective); date and time as reported by mother as soon as satisfactory breastfeeding episode achieved 8. Shock ascertained measured using data collected from EMR at hospital discharge 9. Coagulopathy measured using data collected from EMR at hospital discharge 10. Hysterectomy measured using data collected from EMR at hospital discharge 11. Organ dysfunction measured using data collected from EMR at hospital discharge 12. Maternal death measured using data collected from EMR at hospital discharge 13. Adverse effects of hypertension, fever, vomiting, shivering, epigastric discomfort or fullness, diarrhoea, headache, chest pain, palpitation, and shortness of breath measured using data collected through direct questioning within 24 hours of birth and from EMR 14. Composite adverse effects of at least one of hypertension, fever, vomiting, shivering, epigastric discomfort or fullness, diarrhoea, headache, chest pain, palpitation, and shortness of breath measured using data collected from EMR at hospital discharge 15. Major harm measured using data collected from EMR at hospital discharge: 15.1. Haemorrhagic cerebral vascular event due to hypertension 15.2. Maternal febrile convulsion 15.3. Maternal ICU admission for bleeding complications due to uterine atony |
| Overall study start date | 17/01/2024 |
| Overall study end date | 30/10/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Female |
| Target number of participants | 900 |
| Participant inclusion criteria | 1. Expecting a vaginal delivery 2. Age 18-45 years 3. Term gestation (≥37weeks) 4. Single fetus 5. Cephalic presentation 6. Parity <5 7. Final inclusion for randomization: have achieved vaginal delivery |
| Participant exclusion criteria | 1. Contraindication to oxytocin, misoprostol and ergometrine 2. Known hypertension, cardiovascular, hepatic or hematologic disorders |
| Recruitment start date | 01/02/2025 |
| Recruitment end date | 31/03/2026 |
Locations
Countries of recruitment
- Malaysia
Study participating centre
Kuala Lumpur
59100
Malaysia
Sponsor information
Hospital/treatment centre
Pusat Perubatan Universiti Malaya
Lembah Pantai
Kuala Lumpur
59100
Malaysia
| Phone | +60 (0)3 7967 6686 |
|---|---|
| fomadmin@um.edu.my | |
| Website | https://medicine.um.edu.my/ |
"ROR" |
https://ror.org/00vkrxq08 |
Funders
Funder type
Hospital/treatment centre
Government organisation / Universities (academic only)
- Alternative name(s)
- University of Malaya, University Malaya, Malayan University, UM
- Location
- Malaysia
Results and Publications
| Intention to publish date | 31/01/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The raw data generated during and/or analyzed during the current study are/will be available upon request from Dr Hemavahthy Mani (hemavahthymani@gmail.com) subject to institutional review board approval 6 months after publication. The type of data that will be shared: the reported data Whether consent from participants was required and obtained: yes Comments on data anonymization: yes Any ethical or legal restrictions: Data sharing will be subject to ethical review and approval |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 09/07/2024 | 13/01/2025 | No | Yes | |
| Protocol file | version 3 | 09/07/2024 | 13/01/2025 | No | No |
Additional files
Editorial Notes
13/01/2025: Study's existence confirmed by the Medical Research Ethics Committee, University Malaya Medical Centre.
