Efficacy of Carbetocin in Prevention of Postpartum Hemorrhage in Obese Versus Non Obese Women

Efficacy of Carbetocin at Elective Cesarean Section in Prevention of Postpartum Hemorrhage in Obese Versus Non-obese Women, A Randomized Controlled Clinical Trial

Postpartum hemorrhage [PPH] can have serious consequences and is the leading cause of maternal mortality globally. Uterine contractility plays an important role in post-delivery uterine involution; impaired contractility can contribute to PPH. Should contractility be impaired among obese women, there would be implications for management. Therefore, the investigators sought to investigate whether obese women would also experience a need for more uterine agents during the management of an obstetric hemorrhage.

Study Overview

• Status: Completed
• Conditions: Post Partum Hemorrhage; Obesity, Maternal
• Intervention / Treatment: Drug: Carbetocin 100 Microgram/mL Solution for Injection

Detailed Description

The American College of Obstetricians and Gynecologists (ACOG) updated their definition of postpartum hemorrhage (PPH) to be "blood loss greater than or equal to 1000 ml or blood loss accompanied by signs or symptoms of hypovolemia" .

Recent clinical and translational studies have suggested a decrease in uterine contractility among obese and morbidly obese women as a primary cause of obstetric hemorrhage.

In the United States, the prevalence of maternal obesity has been steadily rising, with more than half of pregnant women classified as overweight or obese. A panel of obstetric experts has speculated that the rising prevalence of maternal obesity in developed countries may explain the increase in postpartum hemorrhage incidence.

Uterotonic drugs are recommended to reduce blood loss and the risk of postpartum hemorrhage (PPH) after Cesarean delivery.

There are several prophylactic uterotonic agents available for use, including oxytocin, oxytocin/ergometrine, and carbetocin. Carbetocin is a synthetic analog of oxytocin which provides a longer duration of action than oxytocin (half-life 85-100 min versus 3-4 min).

The investigators aim to investigate the impact of carbetocin on uterine contractility in obese versus non-obese pregnant women undergoing elective cesarean delivery following carbetocin 100 mcg bolus IV administration as a prophylaxis of postpartum hemorrhage in a randomized controlled trial. The incestigators hypothesize that increased volume of distribution reduces the bioavailability of carbetocin and may be an explanation for reduced efficacy. Also the investigators will examine uterine tone as a surrogate marker for the bioavailability of carbetocin.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo
    • Giza, Cairo, Egypt, 11562
      • Shaimaa El Shemy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy women with a singleton pregnancy undergoing a Cesarean delivery after at least 37 completed weeks of gestation under regional anesthesia.
• Aged (18-39) years and with signed informed consent.

Exclusion Criteria:

• Emergency Cesarean Section due to fetal distress.
• Maternal comorbidities such as severe cardiovascular disorders, kidney or liver disorders, coagulopathies, as well as epilepsy.
• Uterine malformation.
• Fetal malformation.
• Known hypersensitivity to carbetocin or oxytocin.
• Uterine overdistention (as in polyhydramnios, twins, and fetal macrosomia)
• Injury of uterine vessels during CS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A: Parturient with BMI ≥ 30 kg/m2.; All patients will receive a bolus of carbetocin 100mcg IV over one minute after cord clamping. [PabalVR, Ferring AG, Baar, Switzerland]).	Drug: Carbetocin 100 Microgram/mL Solution for Injection; All patients will receive a bolus of carbetocin 100mcg IV over one minute after cord clamping. [PabalVR, Ferring AG, Baar, Switzerland]).then assess uterine contractility and postpartum bleeding measuring
Other: Group B: Parturients with BMI < 30kg/m2 (control group); All patients will receive a bolus of carbetocin 100mcg IV over one minute after cord clamping. [Pabal, Ferring , Baar, Switzerland]).	Drug: Carbetocin 100 Microgram/mL Solution for Injection; All patients will receive a bolus of carbetocin 100mcg IV over one minute after cord clamping. [PabalVR, Ferring AG, Baar, Switzerland]).then assess uterine contractility and postpartum bleeding measuring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Blood loss (ml) at cesarean section	Estimation of blood loss will be by assessing difference between pre -operative hemoglobin and a 24 hours after delivery hemoglobin and pre and 24h after delivery hematocrit according to the following formula: Estimated blood volume (pre-operative Hct-postoperative Hct)/pre-operative Hct.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine contractility and the need for more doses of carbetocin	Uterine contractility, the proportion of women receiving additional uterotonics after administration of single dose of carbetocin, transfusion of blood products and use of non-drug measures to treat PPH.	3 months
Estimated Blood loss by weighing gauze towel	weighing gauze towels (grams)pre and postoperative. Using suction when amniotic fluid membranes rupture up to delivery of the placenta. Gauze towels will be used exclusively to mop up the blood until closure of the abdomen	3 months

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Actual): October 25, 2023
• Study Completion (Actual): November 25, 2023

Study Registration Dates

• First Submitted: December 10, 2023
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Obesity; Uterine Hemorrhage; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hemorrhage; Postpartum Hemorrhage; Obesity, Maternal; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Carbetocin
• Other Study ID Numbers: Postpartum hemorrhage, Obesity

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No