Sublingual Misoprostol in Reduction of Caesarean Blood Loss

Study Overview
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Brief Summary
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Caesarean delivery is inevitably associated with a higher amount of blood loss vis-à-vis primary postpartum haemorrhage, when compared to vaginal delivery. Oxytocin use in tropical developing countries for the reduction blood loss at caesarean section have been met with challenges of ineffectiveness due to poor transportation, inadequate storage and drug adulteration. Therefore, there is a need for an effective, temperature stable uterotonic with a lesser risk of adulteration. The study is aimed at evaluating the effectiveness and safety of adjunctive sublingual misoprostol in reducing intraoperative blood loss at caesarean section.

Detailed Description
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It would be a double blind randomized controlled trial. One hundred and fifty-two pregnant women at term who have indications for caesarean section and have risk factors for primary postpartum haemorrhage, as well as meet the eligibility criteria would be randomized equally into two study arms (Misoprostol study arm and Placebo study arm) after informed consent. The Misoprostol study arm will receive 400 mcg of sublingual misoprostol as two 200 mcg misoprostol tablets. The Placebo study arm would receive two sublingual placebo tablets similar to the misoprostol tablets. The Misoprostol and the Placebo tablets will be given in each study arm at the point of starting the uterine incision at caesarean section. Both study arms would receive routine intravenous oxytocin at the time of clamping of the umbilical cord. The outcome measures will be estimated intraoperative blood loss, the need for additional intraoperative oxytocic, blood transfusion, the occurrence of side effects, and incidence of primary postpartum haemorrhage.

Official Title
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Comparison Between Adjunctive Sublingual Misoprostol Versus Adjunctive Placebo in the Reduction of Intraoperative Blood Loss During Caesarean Section

Conditions
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Post Partum Hemorrhage

Intervention / Treatment
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* Drug: Misoprostol
* Drug: Oxytocin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women at term (37+0 weeks to 41+6 weeks gestational age) for elective or non-elective caesarean sections Pregnant women who have risk factor for primary postpartum haemorrhage Pregnant women who consent to participate in the study Exclusion Criteria: Pregnant women who withhold consent to participate in the study Caesarean sections for dire emergencies (umbilical cord prolapse, suspected fetal distress and active antepartum haemorrhage) Previous caesarean sections or other uterine surgeries Pregnant women with no risk factor for primary postpartum haemorrhage Allergy to misoprostol use Known history of hepatic, renal and haematological disorders Caesarean section to be done under general anaesthesia Fever (temperature ≥ 37.5 degrees centigrade) Pre-operative anaemia (pre-operative haematocrit level < 30 %) Pregnant women who are unconscious or have eclampsia
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Misoprostol<br>400 mcg of sublingual misoprostol as two 200 mcg misoprostol tablets at the point of starting the uterine incision at caesarean section, then bolus administration of 10 IU of intravenous oxytocin followed by an infusion of 20 IU of oxytocin in 500 ml of normal saline at a rate of twenty drops per minute to run over eight hours. | Drug: Misoprostol<br>* The misoprostol tablets to be used in the study will be of the same brand and batch<br>Drug: Oxytocin<br>* The oxytocin ampoules to be used in the study will be of the same brand and batch<br>|
| Placebo Comparator: Placebo<br>Two sublingual placebo tablets similar to the misoprostol tablets at the point of starting the uterine incision at caesarean section, then bolus administration of 10 IU of intravenous oxytocin followed by an infusion of 20 IU of oxytocin in 500 ml of normal saline at a rate of twenty drops per minute to run over eight hours. | Drug: Oxytocin<br>* The oxytocin ampoules to be used in the study will be of the same brand and batch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated volume of intraoperative blood loss | Intraoperative blood loss would be estimated by standard volumetric and gravimetric methods using standard calibrated suction bottles for the volumetric method and for the gravimetric method; wet weight of the abdominal mops, delivery mats, theatre drapes, theatre gowns and vaginal swabs will be gotten using the Mettler PB 153 weighing scale after its re-calibration. The total estimated intraoperative blood loss (T) will be measured by calculating the sum total of the weights of the blood soaked abdominal mops, vaginal gauzes, theatre drapes, theatre gowns and delivery mat (S) and subtracting the sum total of the dry weights of the used abdominal mops, vaginal gauzes, theatre drapes, theatre gowns and delivery mat (D) as shown in the equation: T = S - D. It will be assumed that 1 ml of blood weighs approximately 1 g | Immediate postoperative period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Additional intraoperative oxytocic | Additional intraoperative oxytocic as10 IU oxytocin when there is absence of uterine tone as assessed by the lead surgeon ten minutes after administration of the intervention drug. Intramuscular ergometrine at a dose of 0.5 mg will be used as a second-line additional uterotonic agent where there are no contraindications. | From intraoperative administration of the study intervention till 4 hours postoperative | 
| Postoperative blood transfusion | Postoperative blood transfusion indicated by occurrence of primary postpartum haemorrhage (an intraoperative blood loss ≥ 1,000 ml following caesarean section or symptomatic postoperative haematocrit level ≤ 24 %) | From intraoperative administration of the study intervention till 48 hours postoperative | 
| Side effect profile | Side effect including nausea, vomiting, fever, and shivering | From intraoperative administration of the study intervention till 4 hours postoperative | 
| Postoperative haematocrit level | 48 hours postoperative haematocrit level | At 48 hours postoperative |