Prophylactic Methylergonovine for Twin Cesarean

Postpartum Hemorrhage Clinical Trial

Official title:

Prophylactic Methylergonovine in Patients Undergoing Cesarean Delivery With Twin Gestations: A Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05772156
• Other study ID #: AAAU3902
• Status: Recruiting
• Phase: Phase 4
• Start date: March 7, 2023
• Est. completion date: September 30, 2024

Study information

• Verified date: April 2024
• Source: Columbia University
• Contact: Mirella Mourad
• Phone: 212-305-6293
• Email: mjm2246[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: September 30, 2024
• Est. primary completion date: March 3, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Postpartum Hemorrhage
• Pregnancy Complications
• Twin; Complicating Pregnancy

Intervention

Drug:
• Methylergonovine
Methylergonovine 200mcg Intramuscular (IM)
• Placebo
Matching saline placebo

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

References & Publications (8)

Attilakos G, Psaroudakis D, Ash J, Buchanan R, Winter C, Donald F, Hunt LP, Draycott T. Carbetocin versus oxytocin for the prevention of postpartum haemorrhage following caesarean section: the results of a double-blind randomised trial. BJOG. 2010 Jul;117(8):929-36. doi: 10.1111/j.1471-0528.2010.02585.x. Epub 2010 May 19. — View Citation

Blitz MJ, Yukhayev A, Pachtman SL, Reisner J, Moses D, Sison CP, Greenberg M, Rochelson B. Twin pregnancy and risk of postpartum hemorrhage. J Matern Fetal Neonatal Med. 2020 Nov;33(22):3740-3745. doi: 10.1080/14767058.2019.1583736. Epub 2019 Mar 5. — View Citation

Chaudhuri P, Banerjee GB, Mandal A. Rectally administered misoprostol versus intravenous oxytocin infusion during cesarean delivery to reduce intraoperative and postoperative blood loss. Int J Gynaecol Obstet. 2010 Apr;109(1):25-9. doi: 10.1016/j.ijgo.2009.11.009. Epub 2010 Jan 13. — View Citation

Horowitz E, Yogev Y, Ben-Haroush A, Rabinerson D, Feldberg D, Kaplan B. Routine hemoglobin testing following an elective Cesarean section: is it necessary? J Matern Fetal Neonatal Med. 2003 Oct;14(4):223-5. doi: 10.1080/jmf.14.4.223.225. — View Citation

Masse N, Dexter F, Wong CA. Prophylactic Methylergonovine and Oxytocin Compared With Oxytocin Alone in Patients Undergoing Intrapartum Cesarean Birth: A Randomized Controlled Trial. Obstet Gynecol. 2022 Aug 1;140(2):181-186. doi: 10.1097/AOG.0000000000004857. Epub 2022 Jul 6. — View Citation

Osterman M, Hamilton B, Martin JA, Driscoll AK, Valenzuela CP. Births: Final Data for 2020. Natl Vital Stat Rep. 2021 Feb;70(17):1-50. — View Citation

Senturk S, Kagitci M, Balik G, Arslan H, Kir Sahin F. The Effect of the Combined Use of Methylergonovine and Oxytocin during Caesarean Section in the Prevention of Post-partum Haemorrhage. Basic Clin Pharmacol Toxicol. 2016 May;118(5):338-43. doi: 10.1111/bcpt.12500. Epub 2015 Nov 15. — View Citation

Sheehan SR, Montgomery AA, Carey M, McAuliffe FM, Eogan M, Gleeson R, Geary M, Murphy DJ; ECSSIT Study Group. Oxytocin bolus versus oxytocin bolus and infusion for control of blood loss at elective caesarean section: double blind, placebo controlled, randomised trial. BMJ. 2011 Aug 1;343:d4661. doi: 10.1136/bmj.d4661. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in maternal hemoglobin level	The change in maternal hemoglobin level as taken from blood samples. The change will be calculated from preoperative day 1 (baseline) to postoperative day 1.	Baseline and Postoperative Day 1 (Approximately 48 hours)
Secondary	Surgical time	Surgical time measured from the time of incision to closure	Intraoperative (Approximately 24 hours)
Secondary	Estimated blood loss	At the end of the surgery, the primary surgeon will estimate the blood loss throughout the case.	Intraoperative (Approximately 24 hours)
Secondary	Quantitative blood loss	Quantitative blood loss is calculated by weighing the used towels during the operation. The number is calculated by the circulating nurse in the operating room.	Intraoperative (Approximately 24 hours)
Secondary	Number of Participants with Postpartum hemorrhage	The number of participants with postpartum hemorrhage (defined as estimated blood loss >1000 cc)	Intraoperative (Approximately 24 hours)
Secondary	Number of Participants Requiring Use of Uterotonics	Number of participants given uterotonics, such as prostaglandins	Intraoperative (Approximately 24 hours)
Secondary	Number of Participants Requiring Use of Tranexamic acid Use of Tranexamic acid Use of Tranexamic acid	Number of participants given Tranexamic acid	Intraoperative (Approximately 24 hours)
Secondary	Number of Participants Requiring Use of Open-Label Methylergonovine	Number of participants requiring the use of any amount of open-label methylergonovine (not blinded study drug)	Intraoperative (Approximately 24 hours)
Secondary	Number of Participants Requiring Transfusion (Intraoperative)	Number of participants requiring transfusion of 1 or more units of packed red blood cells, including whole blood or cell saver.	Intraoperative (Approximately 24 hours)
Secondary	Composite Number of Surgical or Radiological Interventions	Composite number of surgical or radiological interventions (such as: laparotomy, evacuation of hematoma, hysterectomy, uterine packing, intrauterine balloon tamponade, interventional radiology) to control bleeding and related complications or maternal death.	Intraoperative (Approximately 24 hours)
Secondary	Number of Participants with Transfusion related acute lung injury (TRALI)	Number of participants with transfusion related acute lung injury (TRALI)	6 weeks
Secondary	Number of Participants Requiring Transfusion (6 weeks)	Number of participants requiring transfusion of 1 or more units of fresh frozen plasma, cryoprecipitate, or platelets or administration of any factor concentrates.	6 weeks
Secondary	Number of Participants with Acute Elevation of Serum Creatinine	Number of participants with acute elevation of serum creatinine of = 0.3 mg/dL	48 hours
Secondary	Number of Postpartum Infectious Complications	Number of Postpartum infectious complications such as: endometritis, surgical site infection, pelvic abscess	6 weeks
Secondary	Number of Participants with Admission to the Intensive Care Unit	Number of participants with admission to the intensive care unit for more than 24 hours	6 weeks
Secondary	Length of stay	Length of stay measured from the time of hospital admission to hospital discharge.	5 days
Secondary	Number of Participants Re-Admitted to the Hospital	The number of participants who experienced hospital re-admission	6 weeks
Secondary	Apgar scores	Apgar score is a measure of the physical condition of a newborn infant. Scores range from 0-10 with a higher score indicating a better outcome; 5-minute Apgar score of 0-3 is low, 4-6 is moderately abnormal, and 7-10 is reassuring.	Time of delivery (Approximately 24 hours)
Secondary	Neonatal intensive care unit (NICU) admission	Number of newborns admitted to the neonatal intensive care unit (NICU).	Time of delivery (Approximately 24 hours)