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Comparison of Nifedipine Versus Indomethacin for Acute Preterm Labor

Primary Purpose

Obstetric Labor, Premature

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Nifedipine

Indomethacin

About this trial

This is an interventional treatment trial for Obstetric Labor, Premature focused on measuring Obstetric Labor, Premature, Tocolytic Agents

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

University of California, Los Angeles
University of California, Irvine
University of California, Davis
University of California, San Diego
University of California, San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Nifedipine

Indomethacin

Arm Description

Participants will be given this medication orally

Outcomes

Primary Outcome Measures

Number of Participants With Delay of Preterm Delivery by 48 Hours.

1. To compare the prolongation of pregnancy by 48 hours after women are diagnosed with threatened preterm labor prior to 32 weeks gestational age and treated with either nifedipine or indomethacin. The primary outcome measured will be delay of (preterm delivery) by 48 hours.

Secondary Outcome Measures

Full Information

NCT ID

NCT03129945

First Posted

January 5, 2015

Last Updated

October 7, 2021

Sponsor

University of California, Irvine

Collaborators

University of California, San Francisco, University of California, Davis, University of California, San Diego, University of California, Los Angeles

1. Study Identification

Unique Protocol Identification Number

NCT03129945

Brief Title

Comparison of Nifedipine Versus Indomethacin for Acute Preterm Labor

Official Title

Comparison of Nifedipine Versus Indomethacin for Acute Preterm Labor

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

January 17, 2017 (Actual)

Primary Completion Date

April 18, 2019 (Actual)

Study Completion Date

April 18, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, Irvine

Collaborators

University of California, San Francisco, University of California, Davis, University of California, San Diego, University of California, Los Angeles

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obstetric Labor, Premature

Keywords

Obstetric Labor, Premature, Tocolytic Agents

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nifedipine

Arm Type

Active Comparator

Arm Description

Participants will be given this medication orally

Arm Title

Indomethacin

Arm Type

Active Comparator

Arm Description

Participants will be given this medication orally

Intervention Type

Drug

Intervention Name(s)

Nifedipine

Other Intervention Name(s)

Procardia

Intervention Description

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

Intervention Name(s)

Indomethacin

Other Intervention Name(s)

Indocin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants With Delay of Preterm Delivery by 48 Hours.

Description

Time Frame

Participants will be followed for the duration of the hospital stay, an expected average of 1 week

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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: Associated with cervical change by cervical dilation greater than or equal to 1cm OR effacement greater than or equal to 25 to 50% Cervix greater than or equal to 2cm dilated on initial digital exam At least 75% effaced on initial digital exam 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.

Overall Study Officials: