Comparison of Nifedipine Versus Indomethacin for Acute Preterm Labor

NCT ID: NCT03129945

Last Updated: 2021-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-17
• Study Completion Date: 2019-04-18

Brief Summary

The purpose of this research study is to determine the best medication to stop preterm labor. Recent studies have identify nifedipine and indomethacin as the two medications that are most likely to delay delivery for 48 hours, decrease maternal side effects and decrease some complications related to preterm delivery to the neonate. Both of these medications are commonly used to stop pre-term labor, therefore it has become our institution's standard to use these two medications in the setting of preterm labor. There have been limited studies comparing these two medications directly.

A total of 450 participants will be asked to participate across all study sites.

Detailed Description

There are about 10 million births that occur before 37 weeks (prior to full term gestation) that occur annually worldwide. More than 1 million infants die from complications related to preterm birth. Tocolytics, medications that stop preterm labor, have been well studied. Results regarding prolongation of pregnancy are varied, but tocolytics have been shown to delay delivery for 48 hours, allowing time to administer corticosteroids. ACOG (American Congress of Obstetrics and Gynecologists) recommends giving tocolytics to provide time for corticosteroid administration, transfer to tertiary level care and to allow for magnesium infusion to protect the neonatal brain. Corticosteroid administration when the course is completed (48 hours from first dose) decreases some of the major risks associated with prematurity.

Recent meta-analyses have shown of the commonly used tocolytics, calcium channel blockers and prostaglandin inhibitors ranked consistently among the top three medications in several categories including delaying delivery by 48 hours. There have been only two published randomized control studies to date that have directly compared these two tocolytics. These studies lacked power and standardization to provide clinical guidelines. There is a high neonatal mortality and morbidity along with exceedingly high hospital costs associated with complications related to preterm birth, so it is important to intervene with superior medications. Here the investigators propose a multi institutional (based within the University of California system) randomized controlled study to directly compare nifedipine (most commonly used calcium channel blocker) to indomethacin (most commonly used prostaglandin inhibitor).

Objective:

The Investigator's objective is to compare the prolongation of pregnancy by 48 hours after women are diagnosed with preterm labor prior to 32 weeks gestational age and treated with either nifedipine or indomethacin. Investigators hypothesize that indomethacin will significantly arrest preterm labor by 48 hours in more women compared to nifedipine. The primary outcomes measures will be delaying preterm delivery by 48 hours; secondary outcomes measures will include delay of delivery by 7 days and decreasing delivery before 37 weeks.

Conditions

Obstetric Labor, Premature

Keywords

Obstetric Labor, Premature; Tocolytic Agents

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nifedipine

Participants will be given this medication orally

Group Type: ACTIVE_COMPARATOR

Nifedipine

Intervention Type: DRUG

Subjects will be given nifedipine 10mg orally and repeated every 20 minutes for a maximum dose of 30mg in the first hour followed by 20mg every 6 hours for the first 48 hours.

Indomethacin

Participants will be given this medication orally

Group Type: ACTIVE_COMPARATOR

Indomethacin

Intervention Type: DRUG

Those randomized to indomethacin will be given 100mg orally as a loading dose followed by 50mg every 6 hours for the first 48 hours of treatment.

Interventions

Nifedipine

Subjects will be given nifedipine 10mg orally and repeated every 20 minutes for a maximum dose of 30mg in the first hour followed by 20mg every 6 hours for the first 48 hours.

Intervention Type: DRUG

Indomethacin

Those randomized to indomethacin will be given 100mg orally as a loading dose followed by 50mg every 6 hours for the first 48 hours of treatment.

Intervention Type: DRUG

Other Intervention Names

Procardia; Indocin

Eligibility Criteria

Inclusion Criteria

• Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 140 weeks by gestational age (see dating below) is acceptable.
• Gestational age at randomization between 240 weeks to 315 weeks by using the dating determinations as below
• Preterm labor with intact membranes. Preterm labor is defined as at least 6 regular uterine contractions in 60 minutes either seen on tocodynamometer, palpated by health providers and/or subjectively felt by the patient and at least one of the following:

1. Associated with cervical change by cervical dilation greater than or equal to 1cm OR effacement greater than or equal to 25 to 50%

2. Cervix greater than or equal to 2cm dilated on initial digital exam

3. At least 75% effaced on initial digital exam

4. Short cervical length (defined by each institution's policy) as obtained by transvaginal cervical sonography [in general, this is defined as a measurement of 2.0 - 2.5 cm or less] and/or a positive fetal fibronectin test (defined as a level greater than 50ng/mL).

• Intact membranes
• 18 years of age or older

Exclusion Criteria

• Fetal demise, or known major fetal anomaly, including cardiac anomaly and hydrops
• Maternal contraindication to nifedipine: preload cardiac lesions or maternal hypotension (systolic blood pressure less than 100 or diastolic blood pressure less than 60). A delayed dose can be given if blood pressure improves - it will be documented if dose is delayed, how long from scheduled dose it was delayed and reason for delay.
• Maternal contraindication to indomethacin: platelet dysfunction or bleeding disorders, hepatic dysfunction, gastrointestinal ulcerative disease, renal dysfunction and asthma
• Obstetrical contraindication to tocolysis not already mentioned: non reassuring fetal status, severe preeclampsia or eclampsia, maternal bleeding with hemodynamic instability, chorioamnionitis, preterm premature rupture of membranes
• Participation in another interventional study that influences neonatal morbidity or mortality
• Participation in this trial earlier in the pregnancy
• Maternal allergy to either indomethacin or nifedipine
• Maternal allergy to aspirin and other NSAIDs.
• Maternal hypertension requiring treatment.
• Maternal kidney disorder that would require adjustment in magnesium dosing.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

University of California, Irvine

OTHER

Sponsor Role: lead

Responsible Party

Judith H Chung

MD, Professor, Division of Maternal Fetal Medicine, Dept OBGYN

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Deborah A Wing, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Irvine

Mary Norton, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Gladys (Sandy) Ramos, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Aisling Murphy, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Veronique Tache, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California, Los Angeles

Los Angeles, California, United States

University of California, Irvine

Orange, California, United States

University of California, Davis

Sacramento, California, United States

University of California, San Diego

San Diego, California, United States

University of California, San Francisco

San Francisco, California, United States

Countries

United States

References

Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, Coomarasamy A, Tobias A, Chou D, Oladapo OT, Price MJ, Morris K, Gallos ID. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD014978. doi: 10.1002/14651858.CD014978.pub2.

Reference Type: DERIVED

PMID: 35947046 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UC Reliance 857

Identifier Type: OTHER

Identifier Source: secondary_id

2014-1085

Identifier Type: -

Identifier Source: org_study_id