Indomethacin Versus Nifedipine for Preterm Labor Tocolysis

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00486824
• Collaborator: (none)
• Enrollment: 29
• Location: 1
• Arms: 2
• Actual Duration (Months): 68.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Indomethacin and Nifedipine are commonly used medications for treatment of pre term labor. This study will compare the efficacy and adverse outcomes of oral nifedipine versus oral indomethacin for preterm labor tocolysis in an effort to identify which drug is most effective.

Patients diagnosed with preterm labor who grant consent will be randomized by the pharmacy to receive oral nifedipine or oral indomethacin. Both the patient and primary medical provider will be blinded to the identity of the study drug. An abdominal ultrasound will be performed in the labor and delivery unit prior to the administration of the tocolytic in order to assess fetal position and fluid level, and to document fetal cardiac activity and movement, and will be repeated at 48 hours post-randomization. Following randomization, the patient will be given either 50 mg oral indomethacin with two pills of placebo, or 3 pills each containing 10 mg oral nifedipine for a total of 30 mg. The patients will then receive either 25 mg of oral indomethacin every 6 hours for 48 hours, or 20 mg of oral nifedipine every 6 hours for 48 hours. Tocolysis beyond 48 hours will not be used.

Condition or Disease	Intervention/Treatment	Phase
Obstetric Labor, Premature	Drug: Indomethacin; Drug: Nifedipine	Phase 1/Phase 2

Detailed Description

Patients presenting between 24-34 weeks gestation diagnosed with preterm labor who grant consent will be randomized by the pharmacy to receive oral nifedipine or oral indomethacin. Both the patient and primary medical provider will be blinded to the identity of the study drug. An abdominal ultrasound will be performed in the labor and delivery unit prior to the administration of the tocolytic in order to assess fetal position and fluid level, and to document fetal cardiac activity and movement, and will be repeated at 48 hours post-randomization. Following randomization, the patient will be given either 50 mg oral indomethacin with two pills of placebo, or 3 pills each containing 10 mg oral nifedipine for a total of 30 mg. The patients will then receive either 25 mg of oral indomethacin every 6 hours for 48 hours, or 20 mg of oral nifedipine every 6 hours for 48 hours. Tocolysis beyond 48 hours will not be used. Antibiotics and steroids for fetal lung maturity will be administered as per standard of care for preterm labor. Maternal side effects and delivery outcomes will be assessed from questionnaires administered by the study team following treatment, and/or from review of the patient's medical records.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Indocin Versus Nifedipine for Preterm Labor Tocolysis - A Randomized Double-Blinded Clinical Trial
• Actual Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Dec 8, 2012
• Actual Study Completion Date: Dec 8, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Indomethacin 50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs.	Drug: Indomethacin; One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.
Active Comparator: Nifedipine 30 mg Nifedipine initially followed by 20 mg every 6 hrs for 48 hrs.	Drug: Nifedipine; Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.

Outcome Measures

Primary Outcome Measures

1. Count of Patients With Recurrent Preterm Labor Within Two Weeks of Randomization [Two weeks after enrolled and randomized, up to 37 weeks of pregnancy]

   Preterm labor was defined as documented cervical change and regular uterine contractions at least every 5 minutes, or at least 2 cm cervical dilation and 80% cervical effacement. Preterm labor is defined as uterine contractions occurring up to 37 weeks of pregnancy.

Secondary Outcome Measures

1. Neonatal Birthweight [Until discharge of mother and neonate from delivery hospital, up to 30 days after delivery]

   Birthweight is presented in grams

2. Gestational Age at Delivery [Up to 42 weeks of pregnancy]

3. Days From First Medication Initiation to Delivery as a Measure of Delay in Delivery [Up to 42 weeks of pregnancy]

4. Count of Participants With Neonatal Morbidity [Up to 42 weeks of pregnancy]

   Neonatal morbidity included admission to neonatal intensive care unit, respiratory distress or sepsis.

5. Count of Participants With Side-effect Due to the Medication [Up to 42 weeks of pregnancy]

   Monitored side-effects for this outcome included abdominal pain, blood pressure change, GI-symptoms and skin rash.

6. Time to Uterine Quiescence [Up to 42 weeks of pregnancy]

   Uterine quiescence was defined as six or fewer uterine contractions per hour. Outcome was described as days.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Singleton and twin gestations

• Intact amniotic membranes

• No contra-indications to tocolysis

• 24-34 weeks gestation by last menstrual period and/or ultrasound

• Documented cervical change, and regular painful uterine contractions at least every 5 minutes, or at least 2 cm cervical dilation and 80% effacement

Exclusion Criteria:

• Ruptured amniotic membranes

• Signs/symptoms of chorioamnionitis (maternal temperature greater than 100.4 F/38.0 C, fetal tachycardia, uterine tenderness)

• Non-reassuring fetal heart rate tracings

• Contra-indications to indomethacin or nifedipine

• Contra-indications to tocolysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Deirdre Judith Lyell, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Deirdre Judith Lyell, Associate Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT00486824
• Other Study ID Numbers: 97873
• First Posted: Jun 15, 2007
• Last Update Posted: Oct 1, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Obstetric Labor, Premature; Indomethacin; Nifedipine

Study Results

Participant Flow

Recruitment Details	A total of 29 patients were initially consented and enrolled. Patients were enrolled through December 2012 but protocol remained open until 2018. Due to patient privacy regulations, the data were accessible for only 10 patients.

Arm/Group Title	Indomethacin	Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
Period Title: Overall Study
STARTED	5	5
COMPLETED	3	3
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Indomethacin	Nifedipine	Total
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	5 100%	10 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	26.0	30	26.5
Sex: Female, Male (Count of Participants)
Female	5 100%	5 100%	10 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	5 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Count of Patients With Recurrent Preterm Labor Within Two Weeks of Randomization
Description	Preterm labor was defined as documented cervical change and regular uterine contractions at least every 5 minutes, or at least 2 cm cervical dilation and 80% cervical effacement. Preterm labor is defined as uterine contractions occurring up to 37 weeks of pregnancy.
Time Frame	Two weeks after enrolled and randomized, up to 37 weeks of pregnancy

Outcome Measure Data

Analysis Population Description

Participants with accessible data are included in the analysis. Not all data were accessible due to patient data privacy regulations.

Arm/Group Title	Indomethacin	Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
Measure Participants	5	5
Count of Participants [Participants]	2 40%	1 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indomethacin, Nifedipine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Neonatal Birthweight
Description	Birthweight is presented in grams
Time Frame	Until discharge of mother and neonate from delivery hospital, up to 30 days after delivery

Outcome Measure Data

Analysis Population Description

Participants with accessible data are included in the analysis. Not all data were accessible due to patient data privacy regulations.

Arm/Group Title	Indomethacin	Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
Measure Participants	5	5
Median (Inter-Quartile Range) [grams]	2830	2240

3. Secondary Outcome

Title	Gestational Age at Delivery
Time Frame	Up to 42 weeks of pregnancy

Outcome Measure Data

Analysis Population Description

Participants with accessible data are included in the analysis. Not all data were accessible due to patient data privacy regulations.

Arm/Group Title	Indomethacin	Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
Measure Participants	5	5
Median (Inter-Quartile Range) [weeks]	37.0	34.0

4. Secondary Outcome

Title	Days From First Medication Initiation to Delivery as a Measure of Delay in Delivery
Time Frame	Up to 42 weeks of pregnancy

Outcome Measure Data

Analysis Population Description

Participants with accessible data are included in the analysis. Not all data were accessible due to patient data privacy regulations.

Arm/Group Title	Indomethacin	Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
Measure Participants	5	5
Median (Inter-Quartile Range) [days]	34.0	36.0

5. Secondary Outcome

Title	Count of Participants With Neonatal Morbidity
Description	Neonatal morbidity included admission to neonatal intensive care unit, respiratory distress or sepsis.
Time Frame	Up to 42 weeks of pregnancy

Outcome Measure Data

Analysis Population Description

Participants with accessible data are included in the analysis. Not all data were accessible due to patient data privacy regulations.

Arm/Group Title	Indomethacin	Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
Measure Participants	5	5
Count of Participants [Participants]	2 40%	3 60%

6. Secondary Outcome

Title	Count of Participants With Side-effect Due to the Medication
Description	Monitored side-effects for this outcome included abdominal pain, blood pressure change, GI-symptoms and skin rash.
Time Frame	Up to 42 weeks of pregnancy

Outcome Measure Data

Analysis Population Description

Participants with accessible data are included in the analysis. Not all data were accessible due to patient data privacy regulations.

Arm/Group Title	Indomethacin	Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
Measure Participants	5	5
Count of Participants [Participants]	2 40%	3 60%

7. Secondary Outcome

Title	Time to Uterine Quiescence
Description	Uterine quiescence was defined as six or fewer uterine contractions per hour. Outcome was described as days.
Time Frame	Up to 42 weeks of pregnancy

Outcome Measure Data

Analysis Population Description

Participants with accessible data are included in the analysis. Not all data were accessible due to patient data privacy regulations.

Arm/Group Title	Indomethacin	Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.	30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
Measure Participants	5	4
Median (Inter-Quartile Range) [days]	2.0	2.0

Adverse Events

Time Frame	Up to maternal and neonatal discharge from the delivery hospital, up to 30 days after the delivery.
Arm/Group Title	Indomethacin		Nifedipine
Arm/Group Description	50 mg. oral Indomethacin initially, followed by 25 mg every 6 hrs for 48 hrs. Indomethacin: One 50 mg tablet of Indomethacin plus 2 pills of placebo followed by one 25 mg tablet of oral indomethacin every 6 hrs for 48 hrs.		30 mg Nifedipine initially followed by 10 mg every 6 hrs for 48 hrs. Nifedipine: Three 10 mg tablets of Nifedipine followed by one 20 mg tablet every 6 hrs for 48 hrs.
All Cause Mortality
	Indomethacin		Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Indomethacin		Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Indomethacin		Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		3/5 (60%)
Blood and lymphatic system disorders
Hypotension	0/5 (0%)	0	1/5 (20%)	1
Gastrointestinal disorders
Gastrointestinal symptoms	1/5 (20%)	1	2/5 (40%)	2
Skin and subcutaneous tissue disorders
Skin rash	1/5 (20%)	1	0/5 (0%)	0

Limitations/Caveats

The sample size for the analysis was not reached.

More Information

Certain Agreements

All Principal Investigators ARE 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.