Clinical trial NCT03303235: Intravenous Versus Intramuscular Administration of Methylergonovine for Uterine Contraction in Cesarean Sections
Official title: How's the Tone? Intravenous Versus Intramuscular Administration of Methylergonovine for Uterine Contraction in Cesarean Sections
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Uterine Atony
Uterine Tone Disorders
Postpartum Hemorrhage
Keywords: methylergonovine
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2017-10-05
Enrollment: 0
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The United States is one of the few modern countries in which maternal peripartum mortality continues to rise. One of the three most important causes of maternal mortality is severe hemorrhage. Controlling postpartum uterine tone remains an important role for the obstetric anesthesiologist. 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.

Methylergonovine maleate is a semi-synthetic ergot alkaloid. Methylergonovine(200 mcg) is administered intramuscularly when oxytocin has been administered but has not contracted the uterus sufficiently. It is not without side effects, however. Due to its vasoconstrictive properties, methylergonovine has been shown to elevate blood pressures and is avoided in preeclamptic patients who may not tolerate abrupt increases in blood pressures. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Time to achieve "adequate" uterine tone
timeFrame: 10 minutes
Secondary outcomes:
measure: Dose that achieves "adequate" uterine tone
timeFrame: 3 minutes
measure: Need for additional uterotonic agents
timeFrame: 3 minutes
measure: Frequency of side effects of methylergonovine
timeFrame: 30 minutes
measure: Need for vasopressors
timeFrame: 3 minutes
measure: Estimated blood loss
timeFrame: 2 hours
measure: Computed blood loss
timeFrame: 2 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Karen Lindeman, MD
role: PRINCIPAL_INVESTIGATOR
References: