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WithdrawnNCT03303235Updated Aug 3, 2020

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

An Early Phase 1 interventional study of Methylergonovine in Uterine Atony, Uterine Tone Disorders and Postpartum Hemorrhage, sponsored by Johns Hopkins University. Withdrawn at 1 site in United States. Open to female participants, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-08-03.

Sponsored by Johns Hopkins University · Early Phase 1, Interventional, and Treatment

Why this study was withdrawn
Collaborators left the institution.
Phase
Early Phase 1
Study type
Interventional
Enrollment
0
Allocation
Randomized
Sex
Female
01

Study 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.

Read the 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.

02

Conditions studied

  • Uterine Atony
  • Uterine Tone Disorders
  • Postpartum Hemorrhage

Keywords

  • methylergonovine
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
Female
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Outcomes assessor)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    IV Methergine

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

    Drug: Methylergonovine

  • Active comparator
    Conventional

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

    Drug: Methylergonovine

Interventions

  • DrugMethylergonovine

    IV vs IM

    Also known as: methergine

05

What researchers measure

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.

    Time frame: 10 minutes

Secondary outcomes

  1. Dose that achieves "adequate" uterine tone

    Determining dose that achieves "adequate" uterine tone as defined by obstetricians on a qualitative numerical scale defined prior to the study (0 to 10 with 0 being inability of uterus to contract (i.e. uterine atony) to 10 being fully contracting uterus; "adequate" would be \>5 on the scale)

    Time frame: 3 minutes

  2. Need for additional uterotonic agents

    Quantifying need for additional uterotonic agents as outlined by the postpartum hemorrhage guidelines set forth by ACOG

    Time frame: 3 minutes

  3. Frequency of side effects of methylergonovine

    Determining frequency of side effects of methylergonovine, including blood pressure changes, especially if elevated \>20% preoperative level), headache, nausea, and vomiting

    Time frame: 30 minutes

  4. Need for vasopressors

    To determine if the patient requires a vasopressor (including phenylephrine, ephedrine, epinephrine, norepinephrine or vasopressin)?

    Time frame: 3 minutes

  5. Estimated blood loss

    Utilizing estimated blood loss by suction canister + estimated weight of blood on surgical lap

    Time frame: 2 hours

  6. Computed blood loss

    Calculating changes in hematocrit (Hct preop - Hct postop)

    Time frame: 2 hours

06

Study locations

1 site
  • Johns Hopkins Hospital
    Baltimore, Maryland 21287, United States
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03303235
Lead sponsor
Johns Hopkins University
Responsible party
Sponsor
First posted
Oct 5, 2017
Start date
Jul 2020 (estimated)
Primary completion
Oct 2020 (estimated)
Completion
Dec 2020 (estimated)
Last update
Aug 3, 2020

Study contacts

Karen Lindeman, MD
principal investigator · Johns Hopkins University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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