Comparison of Nifedipine Versus Indomethacin for Acute Preterm Labor

• Sponsor: University of California, Irvine (Other)
• Overall Status: Completed
• CT.gov ID: NCT03129945
• Collaborator: University of California, San Francisco (Other), University of California, Davis (Other), University of California, San Diego (Other), University of California, Los Angeles (Other)
• Enrollment: 36
• Locations: 5
• Arms: 2
• Actual Duration (Months): 27
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Obstetric Labor, Premature	Drug: Nifedipine; Drug: Indomethacin	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of Nifedipine Versus Indomethacin for Acute Preterm Labor
• Actual Study Start Date: Jan 17, 2017
• Actual Primary Completion Date: Apr 18, 2019
• Actual Study Completion Date: Apr 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nifedipine Participants will be given this medication orally	Drug: 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.; Other Names: Procardia
Active Comparator: Indomethacin Participants will be given this medication orally	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.; Other Names: Indocin

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Delay of Preterm Delivery by 48 Hours. [Participants will be followed for the duration of the hospital stay, an expected average of 1 week]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095
2	University of California, Irvine	Orange	California	United States	92868
3	University of California, Davis	Sacramento	California	United States	95817
4	University of California, San Diego	San Diego	California	United States	92103
5	University of California, San Francisco	San Francisco	California	United States	94143

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Deborah A Wing, MD, University of California, Irvine
• Principal Investigator: Mary Norton, MD, University of California, San Francisco
• Principal Investigator: Gladys (Sandy) Ramos, MD, University of California, San Diego
• Principal Investigator: Aisling Murphy, MD, University of California, Los Angeles
• Principal Investigator: Veronique Tache, MD, University of California, Davis

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 17, 2016

More Information

Publications

None provided.

• Responsible Party: Judith H Chung, MD, Professor, Division of Maternal Fetal Medicine, Dept OBGYN, University of California, Irvine
• ClinicalTrials.gov Identifier: NCT03129945
• Other Study ID Numbers: 2014-1085; UC Reliance 857
• First Posted: Apr 26, 2017
• Last Update Posted: Nov 5, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Judith H Chung, MD, Professor, Division of Maternal Fetal Medicine, Dept OBGYN, University of California, Irvine: Obstetric Labor, Premature; Tocolytic Agents
• Additional relevant MeSH terms: Obstetric Labor, Premature; Indomethacin; Nifedipine

Study Results

Participant Flow

Recruitment Details	Study participants were recruited from January 17, 2017, to February 24, 2018.

Arm/Group Title	Nifedipine	Indomethacin
Arm/Group Description	Participants will be given this medication orally 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.	Participants will be given this medication orally 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.
Period Title: Overall Study
STARTED	15	21
COMPLETED	15	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Nifedipine	Indomethacin	Total
Arm/Group Description	Participants will be given this medication orally 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.	Participants will be given this medication orally 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.	Total of all reporting groups
Overall Participants	15	21	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	21 100%	36 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	15 100%	21 100%	36 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%	21 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Delay of Preterm Delivery by 48 Hours.
Description	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.
Time Frame	Participants will be followed for the duration of the hospital stay, an expected average of 1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Indomethacin
Arm/Group Description	Participants will be given this medication orally 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.	Participants will be given this medication orally 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.
Measure Participants	15	21
Count of Participants [Participants]	15 100%	21 100%

Adverse Events

Time Frame	Adverse event data were collected through study completion, for an average of 1 week.
Adverse Event Reporting Description	Adverse event definition did not differ from the clinicaltrials.gov definitions.
Arm/Group Title	Nifedipine		Indomethacin
Arm/Group Description	Participants will be given this medication orally 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.		Participants will be given this medication orally 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.
All Cause Mortality
	Nifedipine		Indomethacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/21 (0%)
Serious Adverse Events
	Nifedipine		Indomethacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Nifedipine		Indomethacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
shortness of breath	1/15 (6.7%)	1	1/21 (4.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.