Intrauterine Misoprostol Versus Rectal Misoprostol in Reducing Blood Loss During Cesarean Section

The Efficacy and Safety of Intrauterine Misoprostol Versus Rectal Misoprostol in Reducing Blood Loss During and After Cesarean Section

98 pregnant women attending for CS will be randomized into 2 groups. Rectal misopristol group who will receive 400 microgram misoprostol rectally preoperatively with urinary catheter insertion and intrauterine misopristol group will receive 400 microgram misoprostol intrauterine (200 microgram at each cornu) intraoperatively following the delivery of the placenta. The estimated blood loss for each patient will be measured and data of both groups will be compared.

Study Overview

• Status: Unknown
• Conditions: Hemorrhage, Postpartum
• Intervention / Treatment: Drug: Misoprostol

Detailed Description

The study we will include (98) pregnant women attending for cesarean delivery in the Kasr Elaini hospital (faculty of medicine - Cairo university).After signing informed written consent, all participants will be subjected to: Full medical history(including full obstetric history and current pregnancy history and the 1st day of last menstrual period), thorough clinical examination (general and full obstetric examination), obstetric ultrasonography (to confirm gestational age and the eligibility of the current pregnancy to participate in the study) and preoperative laboratory tests (including prothrombin time, prothrombin concentration, complete blood count, and liver and kidney function tests).

Group allocation: On the day of the cesarean delivery, participants will be randomly assigned in a 1:1 ratio into two groups; group A (Rectal misoprostol) and group B (Intrauterine misoprostol). Randomization will be performed using computer-generated random numbers and only the participants will be masked to the group allocation.

Group A (Rectal misoprostol - n=49) will receive 400 microgram misoprostol rectally preoperatively with urinary catheter insertion while group B (Intrauterine misoprostol n=49) will receive 400 microgram misoprostol (cytotec, Pfizer, G.D. Searle LLC) inserted intrauterine (200 microgram at each cornu) intraoperatively following the delivery of the placenta.

Following the delivery of the baby, patients in both groups will receive an intravenous bolus of 5 IU oxytocin (Syntocinon, Novartis, Basel, Switzerland) and 20 IU oxytocin in 500 mL lactated Ringer's solution (infused at a rate of 125 mL/h).

All cesarean sections will be done under spinal anesthesia by the following operative steps: pfannenstiel incision, transverse lower uterine segment incision, immediate cord clamping (< 30 seconds) and the placenta will be removed by controlled cord traction after its spontaneous separation, closure of uterus in 2 layers, closure of anterior abdominal wall in anatomical manner (adequate hemostasis will be ensured in all operative steps).

The number and the difference of weight of operative towels (before and after CS) and amount of blood in suction unit will be recorded.

The estimated blood loss for each patient will be measured and data of both groups will be compared.

In group A, the time interval between rectal misoprostol insertion and fetal delivery will be recorded together with the neonatal outcome (APGAR at 1 and 5 minutes, NICU admission and neonatal death).

Fluid monitoring will be performed through rate of infusion and urine output. A complete blood count test will be performed 12 hours after delivery.

All patients will be followed up for 24 hours following the delivery as regard occurrence of primary postpartum hemorrhage, the need for blood transfusion, misoprostol-related side effects in the first 6 hours (i.e. shivering, pyrexia more than 38 degree Centigrate, headache, nausea, vomiting with or without the need for anti-emetic drugs).

• Study Type: Interventional
• Enrollment (Anticipated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: MOUTAZ ELSHERBINI, MD; Phone Number: (+2)01001588300; Email: mizosherbini@yahoo.com
• Study Contact Backup: Name: Mirna mohamed awad, MSc; Phone Number: (+2)01001401172; Email: mirnaawad91.ma@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Faculty of Medicine - Cairo University
    • Contact: moutaz el sherbini, MD; Phone Number: (+2)01001588300; Email: mizosherbini@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women candidate for CS.
• Full term singleton living pregnancies (> 37 weeks confirmed by the 1st day of the LMP or 1st trimesteric ultrasound scan).
• Spinal or epidural anesthesia for the CS.

Exclusion Criteria:

• Maternal Anemia (hemoglobin <9 g%)
• Maternal medical disorders (e.g. cardiac, renal, and hepatic diseases, or coagulopathies).
• Fetal anomalies or IUGR (estimated fetal weight below the 5th centile)
• Risk of obstetric hemorrhage (e.g. peripartum hemorrhage, abnormal placentation, previous history of uterine atony or postpartum hemorrhage).
• Women attending for emergency CS.
• More than 2 previous CS procedures.
• Prolonged procedure (more than 2 hours from skin incision to skin closure).
• History of prostaglandin allergy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: rectal misopristol; will receive 400 microgram misoprostol rectally preoperatively with urinary catheter insertion.	Drug: Misoprostol; 400 microgram (2 tablets) misoprostol ( cytotec, Pfizer, G.D. Searle LLC) inserted rectally (before CS) in rectal group or intrauterine (200 microgram at each cornu) intraoperatively following the delivery of the placenta in intrauterine group.; Other Names: cytotec
Active Comparator: intrauterine misopristol; will receive 400 microgram misoprostol inserted intrauterine (200 microgram at each cornu) intraoperatively following the delivery of the placenta.	Drug: Misoprostol; 400 microgram (2 tablets) misoprostol ( cytotec, Pfizer, G.D. Searle LLC) inserted rectally (before CS) in rectal group or intrauterine (200 microgram at each cornu) intraoperatively following the delivery of the placenta in intrauterine group.; Other Names: cytotec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
estimated blood loss during and after CS	EBL= EBV x { (Preoperative hematocrit - Postoperative hematocrit) ÷ Postoperative hematocrit} Where EBV is estimated blood volume of the patient in mL (equals weight in kg × 85).	within 12 hours after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
estimated blood loss during CS	The number of operative towels used - The difference of weight of operative towels (before and after cs) plus the amount of blood in suction unit (we will calculate 1 gram of weight difference equal to 1 ml blood loss).	within the CS procedure
Use of additional ecbolics denoting uterine atony	additional 5 IU intravenous bolus oxytocin and 1mL [0.2 mg] intramuscular ergometrine with or without 600 microgram rectal misoprostol postoperatively)	within CS procedure
The occurrence of any maternal side effects (in both groups)	shivering, pyrexia >38C0, headache, nausea, vomiting with or without the need for antiemetic drugs	within 24 hours after the CS procedure
The occurrence of any fetal side effects (rectal group only)	APGAR at 1 and 5 minutes, NICU admission and neonatal death	within 24 hours after the CS procedure

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: moutaz elsherbini, MD, Assistant Professor of obstetrics and gynecology

Publications and helpful links

General Publications

• El-Sherbini MM, Maged AM, Helal OM, Awad MO, El-Attar SA, Sadek JA, ElKomy R, Dawoud MA. A comparative study between preoperative rectal misoprostol and intraoperative intrauterine administration in the reduction of blood loss during and after cesarean delivery: A randomized controlled trial. Int J Gynaecol Obstet. 2021 Apr;153(1):113-118. doi: 10.1002/ijgo.13426. Epub 2020 Nov 6.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2018
• Primary Completion (Anticipated): April 15, 2020
• Study Completion (Anticipated): May 15, 2020

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Cesarean section; hemorrhage; misopristol
• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Gastrointestinal Agents; Reproductive Control Agents; Anti-Ulcer Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Oxytocics; Misoprostol
• Other Study ID Numbers: 1121980

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No