Clinical trial NCT05772156: Prophylactic Methylergonovine for Twin Cesarean
Official title: Prophylactic Methylergonovine in Patients Undergoing Cesarean Delivery With Twin Gestations: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Twin; Complicating Pregnancy
Postpartum Hemorrhage
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2023-03-16
Enrollment: 66
Sex: FEMALE
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Obstetrical hemorrhage (excessive bleeding related to pregnancy) is a leading cause of maternal morbidity (disease or symptom of disease) and mortality (death) worldwide with a significantly higher frequency and severity following cesarean delivery. Twin gestations (twin pregnancy) are at particularly higher risk for postpartum hemorrhage, yet the management of obstetrical bleeding following twin delivery remains identical to singleton delivery.

The purpose of this study is to understand the effect of prophylactic methylergonovine on blood loss in scheduled twin pregnancy cesarean deliveries. Participants will be randomized (like tossing a coin) to Methylergonovine (investigational drug) or water with salt (saline) (placebo). Methylergonovine or saline will be given as an injection immediately after delivery.

Detailed description: Obstetrical hemorrhage is a leading cause of maternal morbidity and mortality worldwide with a significantly higher frequency and severity following cesarean delivery. In 2020, 31.9 percent of pregnant women in the United States underwent cesarean delivery, making it the second most common operation performed. Though multiple complications can occur following cesarean delivery, hemorrhage morbidities are among the most common with significant cardiovascular implications. Twin gestations are at particularly higher risk for postpartum hemorrhage due to impaired myometrial contractility and atony following overdistention; increased maternal blood volume; and increased uterine blood flow compared to singletons, yet the management of obstetrical bleeding following twin delivery remains identical to singleton delivery. Current strategies to address intrapartum hemorrhage have relied on pharmacological and mechanical treatments after intraoperative identification. However, there is extensive work on prophylactic therapies administered intraoperatively to prevent obstetrical hemorrhage. Recent evidence has emerged about the utility of prophylactic Methylergonovine for the prevention of obstetrical hemorrhage. Methylergonovine, a semisynthetic ergot alkaloid, acts primarily on alpha adrenergic receptors of uterine and vascular smooth muscle, increasing uterine tone and promoting vasoconstriction. In a randomized trial of 80 women undergoing intrapartum cesarean delivery found that fewer patients who were allocated to the methylergonovine group received additional uterotonic agents (20% vs 55%, relative risk (RR) 0.4, 95% confidence interval (CI) 0.2-0.6). Participants receiving methylergonovine were more likely to have satisfactory uterine tone (80% vs 41%, RR 1.9, 95% CI 1.5-2.6), lower incidence of postpartum hemorrhage (35% vs 59%, RR 0.6, 95% CI 0.4-0.9), lower mean quantitative blood loss (967 mL vs 1,315 mL; mean difference 348, 95% CI 124-572), and a lower frequency of blood transfusion (5% vs 23%, RR 0.2, 95% CI 0.1-0.6). Investigators concluded that the administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents. In a prospective study of 1210 participants found that intraoperative, prophylactic methylergonovine decreased post-operative blood loss with no adverse side effects. Randomized trials of Methylergonovine as prophylaxis to prevent hemorrhage in cesarean delivery have exclude twin gestations. Currently, there remains a paucity of research regarding prophylactic procedures for twin cesarean delivery. There is an opportunity to prophylactically address hemorrhage in high-risk groups. Therefore, the investigators propose a prospective randomized controlled trial which will compare maternal blood loss associated with prophylactic methylergonovine during cesarean delivery among patients with twin.

Eligibility criteria: Inclusion Criteria:

* Twin gestation
* Scheduled cesarean delivery (\>=34 weeks)

Exclusion criteria:

* Patients with known hypertensive disease: history of chronic hypertension, gestational hypertension or preeclampsia with or without severe features
* Use of protease inhibitors given known vasoconstrictive side effects with concomitant methylergonovine administration
* Hypersensitivity to methylergonovine or any of the ingredients
* Participating in another intervention study where the primary outcome includes postpartum bleeding or thromboembolism, or the study intervention directly affects postpartum bleeding or thromboembolism
* Receipt of uterotonics, other than oxytocin, or planned or expected use of uterotonic prophylaxis
* Non-elective cesarean delivery

Primary outcomes:
measure: Change in Maternal Hemoglobin Level
timeFrame: Baseline and Postoperative Day 1 (Approximately 48 hours)
Secondary outcomes:
measure: Surgical Time
timeFrame: Intraoperative (Approximately 24 hours)
measure: Estimated Blood Loss
timeFrame: Intraoperative (Approximately 24 hours)
measure: Quantitative Blood Loss
timeFrame: Intraoperative (Approximately 24 hours)
measure: Number of Participants With Postpartum Hemorrhage
timeFrame: Intraoperative (Approximately 24 hours)
measure: Number of Participants Requiring Use of Uterotonics
timeFrame: Intraoperative (Approximately 24 hours)
measure: Number of Participants Requiring Use of Tranexamic Acid
timeFrame: Intraoperative (Approximately 24 hours)
measure: Number of Participants Requiring Use of Open-Label Methylergonovine
timeFrame: Intraoperative (Approximately 24 hours)
measure: Number of Participants Requiring Transfusion (Intraoperative)
timeFrame: Intraoperative (Approximately 24 hours)
measure: Number of Participants With Surgical or Radiological Interventions
timeFrame: Intraoperative (Approximately 24 hours)
measure: Number of Participants With Transfusion Related Acute Lung Injury (TRALI)
timeFrame: 6 weeks
measure: Number of Participants Requiring Transfusion (6 Weeks)
timeFrame: 6 weeks
measure: Number of Participants With Acute Elevation of Serum Creatinine
timeFrame: 48 hours
measure: Number of Postpartum Infectious Complications
timeFrame: 6 weeks
measure: Number of Participants With Admission to the Intensive Care Unit
timeFrame: 6 weeks
measure: Length of Stay
timeFrame: Up to 6 weeks
measure: Number of Participants Re-Admitted to the Hospital
timeFrame: 6 weeks
measure: Apgar Scores
timeFrame: 1 and 5 minutes post-delivery (approximately 24 hours post-baseline)
measure: Neonatal Intensive Care Unit (NICU) Admission
timeFrame: Time of delivery (Approximately 24 hours)
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Mirella Mourad
role: PRINCIPAL_INVESTIGATOR
References:
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