Clinical trial NCT03755531: Carbetocin Versus Oxytocin for the Prevention of Postpartum Hemorrhage in Emergency Caesarean Delivery
Official title: Heat Stable Carbetocin Versus Oxytocin for the Prevention of Primary Postpartum Hemorrhage in Emergency Caesarean Delivery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postpartum Hemorrhage (Primary)
Keywords: Oxytocin
Carbetocin
Emergency Caesarean Section
Lead sponsor: Al-Kindy College of Medicine
Sponsor class: OTHER
Collaborators: name: Elweyia Maternity Teaching Hospital
First posted: 2018-11-28
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: PREVENTION

Brief summary: Postpartum haemorrhage keeps to be the leading cause of maternal mortality in middle and low-income countries, including Iraq. Much advancement had been made in the field of treatment for postpartum haemorrhage but no much progress had been made in the field of prevention, where one of its main component is the administration of uterotonic, preferably oxytocin, immediately after birth of the baby.

In many low- and middle income countries, the efficacy of oxytocin cannot be assured since access to sustained cold-chain is unavailable. Regarding the other uterotonics; ergometrine degrades when exposed to heat or light. Misoprostol degrades rapidly when exposed to Moisture.

Innovation in the manufacture of carbetocin had meet the stability requirements for hot and humid climates.

This study had been accomplished to evaluate the uterotonic effect of carbetocin compared with oxytocin for the prevention of postpartum haemorrhage in emergency caesarean delivery. Looking if carbetocin is superior to oxytocin in term of reduction in the need for additional uterotonic agents or the occurrence of PPH.

Detailed description: Setting and design:

It is a double blinded randomized parallel clinical trial. That had been conducted at Al Elweyia Maternity Teaching Hospital in Baghdad during the period from Jan., 4th, 2018 to August, 1st, 2018. Written consent was insured for all the participants.

Data collection:

Three hundred and twenty pregnant women who were underwent emergency caesarean sections under regional anesthesia were enrolled in the study (due to limitation of carbetocin ampoules that were available). Those women were randomized to oxytocin or carbetocin in a rate of 2:1 (for prophylaxis of PPH in the active management of third stage of labour). Twenty cases were omitted since they were not fulfilled the eligibility criteria and only three hundred women were completed the study. They were divided into two groups:

Group1 (case group): 100 pregnant women, whom they received carbetocin for the prevention of PPH.

Group 2 (control group): 200 pregnant women, whom they received oxytocin for the prevention of PPH.

Additional information including age, parity, past medical history, and body mass index (BMI) were taken.

Intervention:

The following steps were followed:

1. Hemoglobin and hematocrit were assessed before caesarean section.
2. One ml of either carbitocin (100 mcg) or oxytocin (10 IU) was given as a bolus intravenous injection by the anesthesiologist after labor of the baby at once.
3. The placentae were delivered by controlled cord traction.
4. It was the operating obstetrician decision to evaluated the uterine tone, bleeding intra-operatively and the need for an additional uterotonic and method of its administration, dose and duration.
5. Our center usual regimen for uterine atony is an oxytocin (40 IU in 500 ml isotonic crystalloid solution) intravenous infusion over 4-5 hours.

Follow up:

For 24 hours was done, that is include:

1. Evaluation of blood loss by the obstetrician and the anesthesiologist after skin closure, that is include the entire amount that had been suctioned, taken by the surgical gauzes or spilled in the surgical field, using visual estimation chart for assessment of blood loss.
2. The need of any additional uterotonic drugs after the operation was recorded.
3. The need of blood transfusion post delivery.
4. The blood pressure and pulse rate of the women involved in the study were documented at 0, 5, 10, 20, 30 and 60 minutes after the injection of the drug.
5. The period of operation (skin cut into the final closure of the skin) was recorded.
6. Intravenous fluid infusion was administered regularly and as it had been stated by the obstetricians and maintained after the operation until oral intake was started.
7. Hemoglobin and hematocrit was assessed the day after the caesarean section.

Statistical analysis:

Statistical Package for Social Sciences (SPSS) version 21 was used. Descriptive statistics presented as (mean ± standard deviation) and frequencies as percentages. The database was examined for errors using range and logical data cleaning methods, and inconsistencies were remedied. Chi square test was used to compare between categorical variables (Fishers exact test used when expected variable was less than 20% of total) and t-test was used to compare between two means. Cohen's d, a standardized measure of effect size for difference between 2 means, which can be compared across different variables and studies, since it has no unit of measurement was used. Significance level was set at P \< 0.05.

Eligibility criteria: Inclusion Criteria:

* Patients age ≥18 years
* Singleton pregnancy
* Full term gestation
* Emergency cesarean section during labor

Exclusion Criteria:

* Cases of coagulopathy
* Drug hypersensitivity
* Medical diseases as; cardiac, hypertension, liver, renal or endocrine diseases
* Uterine fibroids
* Suspected placental pathology (accreta, previa or abruptio)
* General anesthesia
* Longitudinal uterine incision

Primary outcomes:
measure: Blood loss equal or more than 1000 ml
timeFrame: During the first 24 hours
measure: Use of additional uterotonics
timeFrame: During the first 24 hours
Secondary outcomes:
measure: Blood pressure changes in carbetocin versus oxytocin group
timeFrame: Within one hour after administration of the drugs
measure: Pulse rate changes in carbetocin versus oxytocin group
timeFrame: Within one hour after administration of the drugs
measure: Blood transfusion need
timeFrame: During the first 24 hours
Other outcomes:
Locations:
city: Baghdad
country: Iraq
facility: Al Kindy College of Medicine/ University of Baghdad
Study officials:
affiliation: Al Kindy College of Medicine, University of Baghdad
name: Taghreed K Alhaidari, CABOG
role: STUDY_CHAIR
affiliation: Al- Elweyia Maternity Teaching Hospital
name: Shayma S Al-Zubaidy, FICOG, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Al- Elweyia Maternity Teaching Hospital
name: Alaa A Hussein, FICOG, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Al- Elweyia Maternity Teaching Hospital
name: Ulfat M Alnakkash, CABOG
role: PRINCIPAL_INVESTIGATOR
affiliation: Baghdad College of Medicine/ University of Baghdad
name: Ahmed S Alnuaimi, PhD
role: PRINCIPAL_INVESTIGATOR
References: