Intravenous Versus Intramuscular Administration of Methylergonovine for Uterine Contraction in Cesarean Sections

NCT03303235 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: IRB00120873
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Insufficient uterine tone resulting in atony can potentiate hemorrhage and adverse outcomes for the parturient. Oxytocin is the first pharmacologic agent used, followed by methylergonovine, carboprost, and misoprostol. The American Congress of Obstetricians and Gynecologists (ACOG) recommends the sequential use of oxytocin, followed by methylergonovine, carboprost, misoprostol, then surgical intervention for cases of refractory uterine atony. Many studies have examined the effect and dosage of intravenous uterotonics, including oxytocin. Although there are anecdotal reports of using intravenous bolus or rapid infusion of methylergonovine, no randomized trial has compared efficacy and side effects of these two routes of administration. Investigators hypothesize that intravenous methylergonovine reduces the time to adequate uterine tone (the tone at which the uterus is adequately contracted to prevent atony after delivery of neonate), decreases the total dose of methylergonovine to contract the uterus, and therefore produces fewer side effects of hypertension, nausea, and vomiting. Reducing the time to achieve adequate uterine tone is likely to decrease postpartum hemorrhage.

Conditions

Uterine Atony; Uterine Tone Disorders; Postpartum Hemorrhage

Keywords

methylergonovine

Outcome Measures

Primary Outcomes (1)

• Time to achieve "adequate" uterine tone

  Our primary objective is to determine the time to achieve "adequate" uterine tone with either intramuscular (IM) dose versus intravenous (IV) dose methylergonovine, when oxytocin has failed to do so in cesarean sections.

  10 minutes

Secondary Outcomes (6)

• Dose that achieves "adequate" uterine tone

  3 minutes

• Need for additional uterotonic agents

  3 minutes

• Frequency of side effects of methylergonovine

  30 minutes

• Need for vasopressors

  3 minutes

• Estimated blood loss

  2 hours

Study Arms (2)

IV Methergine

EXPERIMENTAL

IV methylergonovine group -IM 0.9% NaCl (1 ml)) + IV methylergonovine (2 mcg/ml) infusion (100 ml)

Drug: Methylergonovine

Conventional

ACTIVE COMPARATOR

IM methylergonovine group -200 mcg IM methylergonovine (1 ml) + IV 0.9% NaCl infusion (100 ml)

Drug: Methylergonovine

Interventions

Methylergonovine DRUG

IV vs IM

Also known as: methergine

Conventional; IV Methergine

Eligibility Criteria

• Gender Eligibility Details: Female parturients eligible to undergo a cesarean section
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients admitted for elective cesarean section
• All laboring patients for planned vaginal delivery as these women may have an unplanned cesarean delivery for maternal or for fetal indications
• Patients not in labor but admitted for non-elective cesarean section
• Administration of oxytocin prior to administration of methylergonovine, in accordance to the ACOG guideline for postpartum hemorrhage
• Obstetrician's request for methylergonovine intraoperatively to the anesthesiologist

You may not qualify if:

• Fetus not considered to be of viable gestational age by obstetrical team
• Patients with hypertension (either chronic or pregnancy-induced, including preeclampsia)
• Patients with coronary artery disease, established and diagnosed by medical internist or cardiologist
• Patients taking CYP3A4 inhibitors
• Patients taking beta blockers.
• Patients with contraindications to any of the uterotonic agents for whatever medical reason (allergies, for example)
• Surgeon request for administration of methylergonovine earlier than per protocol due to clinical situation as abovementioned
• Maternal or obstetrician refusal
• Patients who require obstetrical intervention before 30 minutes has elapsed

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Uterine Inertia; Postpartum Hemorrhage

Interventions

Methylergonovine

Condition Hierarchy (Ancestors)

Dystocia; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ergonovine; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Karen Lindeman, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The patient and obstetrician will all be blinded to group assignments. The anesthesiologist will make and administer the medication, as it is important for timely administration of the methylergonovine when it is asked to be used. The anesthesiologist directly taking care of the patient will not be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: October 5, 2017
• Study Start: July 1, 2020
• Primary Completion: October 1, 2020
• Study Completion: December 1, 2020
• Last Updated: August 3, 2020

Record last verified: 2020-07

Locations

US (1)