Nifedipine or Nifedipine Plus Indomethacin for Treatment of Acute Preterm Labor

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02438371
• Collaborator: (none)
• Enrollment: 49
• Location: 1
• Arms: 2
• Actual Duration (Months): 53.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Tocolytic agents are used for the treatment of preterm labor. It is unclear whether combination treatments of two tocolytic agents are more effective in stopping preterm labor compared to one. Therefore, the investigators propose a comparative effective trial of nifedipine plus indomethacin vs. nifedipine alone for the treatment of preterm labor

Condition or Disease	Intervention/Treatment	Phase
Preterm Labor	Drug: Nifedipine; Drug: Indomethacin	Phase 4

Detailed Description

The investigators current treatment for preterm labor has not been shown to be effective in prolonging pregnancy sufficiently to improve neonatal outcomes and other treatment strategies are needed. Multiple examples demonstrate that multi-agent treatments are routine clinical practice in other fields of medicine including chemotherapeutics for cancer, multi-therapeutics for myocardial infarction and broad spectrum antibiotics for pneumonia. At this time, it is unclear if a combination of tocolytic medications for preterm labor is more advantageous for women. If pregnancy is prolonged with combined tocolytic therapy, this could directly influence the treatment of preterm labor and potentially improve neonatal outcomes. There currently are no trials of combination regimens using widely used tocolytic agents, such as nifedipine and indomethacin. Thus, we propose a comparative effective trial of nifedipine plus indomethacin vs. nifedipine alone for the treatment of preterm labor

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Nifedipine Alone or Nifedipine Plus Indomethacin for Treatment of Acute Preterm Labor: An Open Label, Randomized Comparative Effectiveness Controlled Trial
• Actual Study Start Date: May 1, 2015
• Actual Primary Completion Date: Oct 10, 2019
• Actual Study Completion Date: Oct 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nifedipine Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours for a total of 48 hours.	Drug: Nifedipine; Other Names: Procardia
Active Comparator: Nifedipine plus Indomethacin Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours for a total of 48 hours.	Drug: Nifedipine; Other Names: Procardia ; Drug: Indomethacin

Outcome Measures

Primary Outcome Measures

1. Number of Maternal Participants Who Achieve 48 Hours of Pregnancy Prolongation [48 hours after administration of tocolytic agent]

Secondary Outcome Measures

1. Number of Maternal Participants Who Achieve 7 Days of Pregnancy Prolongation [7 days after administration of tocolytic agent]

2. Number of Days From First Dose of Tocolytic Agent to Delivery [from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)]

   Length of time from tocolytic initiation to the time of delivery

3. Neonatal Birthweight [at the time of birth]

4. Neonatal Sex [at the time of birth]

5. Number of Neonates Who Were Admitted to the Neonatal Intensive Care Unit (NICU) [from birth until hospital discharge or day 120 of life (whichever occurs first)]

6. Neonatal Length of Stay in NICU [from birth until hospital discharge or day 120 of life (whichever occurs first)]

7. Neonatal Length of Hospital Stay [from birth until hospital discharge or day 120 of life (whichever occurs first)]

8. Number of Neonatal Deaths [from birth until hospital discharge or day 120 of life (whichever occurs first)]

9. Number of Neonates With Intraventricular Hemorrhage Diagnosed Using Cranial Ultrasonography [from birth until hospital discharge or day 120 of life (whichever occurs first)]

10. Number of Neonates With Necrotizing Enterocolitis [from birth until hospital discharge or day 120 of life (whichever occurs first)]

11. Number of Neonates With Culture-positive Sepsis [from birth until hospital discharge or day 120 of life (whichever occurs first)]

12. Number of Neonates With Seizures [from birth until hospital discharge or day 120 of life (whichever occurs first)]

13. Number of Neonates Who Needed Mechanical Ventilation [from birth until hospital discharge or day 120 of life (whichever occurs first)]

14. Neonatal Duration of Ventilator Use [from birth until hospital discharge or day 120 of life (whichever occurs first)]

15. Number of Neonates Who Received Continuous Positive Airway Pressure (CPAP) [from birth until hospital discharge or day 120 of life (whichever occurs first)]

16. Number of Maternal Participants Who Delivered by Cesarean Delivery [at the the time of birth]

17. Number of Maternal Participants Who Had Clinical Chorioamnionitis [from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)]

18. Number of Maternal Participants Who Had Preterm Premature Rupture of Membranes (PPROM) [from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)]

19. Number of Maternal Participants Who Had Preeclampsia [from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)]

20. Number of Maternal Participants Who Needed Blood Transfusion [from time of birth to time of discharge from hospital (about 2-3 days)]

21. Number of Maternal Participants With Headache [from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)]

22. Number of Maternal Participants With Nausea [from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)]

23. Number of Maternal Participants With Vomiting [from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)]

24. Number of Maternal Participants With Acid Reflux [from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)]

25. Number of Maternal Participants With Hypotension [from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)]

26. Number of Maternal Participants With Tachycardia [from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)]

27. Number of Maternal Participants With Syncope [from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• We will include pregnant women between 22 0/7 to 31 6/7 weeks gestation who present with regular uterine contractions defined as at least one contraction every 10 minutes for 30 minutes with at least one of the following:

• cervical change of at least 1 cm or

• cervical dilation of 2 cm at the time of initial exam or

• positive fetal fibronectin and transvaginal cervical length <2.5 cm

Exclusion Criteria:

• We will exclude pregnant women with any contraindication to tocolysis:

• clinical chorioamnionitis (defined as a temperature of >100.4 F and any of the following: fundal tenderness, maternal tachycardia, fetal tachycardia or purulent vaginal discharge)

• non reassuring fetal heart tones

• suspected placental abruption

• preterm premature rupture of membranes

• prior tocolytic treatment during the past 48 hours

• known adverse effect to indomethacin or nifedipine

• already receiving nifedipine for chronic hypertension

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Hermann Hospital Texas Medical Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston

Investigators

• Study Director: Maria Hutchinson, M.S., The University of Texas Health Science Center, Houston

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 2, 2018

More Information

Publications

None provided.

• Responsible Party: Jerrie Refuerzo, Associate Professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT02438371
• Other Study ID Numbers: HSC-MS-15-0134
• First Posted: May 8, 2015
• Last Update Posted: Nov 24, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Jerrie Refuerzo, Associate Professor, The University of Texas Health Science Center, Houston: pregnancy; preterm labor; tocolysis
• Additional relevant MeSH terms: Premature Birth; Obstetric Labor, Premature; Indomethacin; Nifedipine

Study Results

Participant Flow

Pre-assignment Detail	The numbers listed in the Participant Flow section correspond to maternal participants.

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Period Title: Overall Study
STARTED	24	25
Received Intervention	24	25
COMPLETED	20	22
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin	Total
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.	Total of all reporting groups
Overall Participants	20	22	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.0 (7.5)	28.5 (7.7)	28.3 (7.6)
Sex: Female, Male (Count of Participants)
Female	20 100%	22 100%	42 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
African/African American/Black American	9 45%	15 68.2%	24 57.1%
Asian	1 5%	0 0%	1 2.4%
Hispanic	7 35%	6 27.3%	13 31%
White	3 15%	1 4.5%	4 9.5%
Region of Enrollment (Count of Participants)
United States	20 100%	22 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Number of Maternal Participants Who Achieve 48 Hours of Pregnancy Prolongation
Time Frame	48 hours after administration of tocolytic agent

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 in the Nifedipine arm.

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	16	22
Count of Participants [Participants]	15 75%	20 90.9%

2. Secondary Outcome

Title	Number of Maternal Participants Who Achieve 7 Days of Pregnancy Prolongation
Time Frame	7 days after administration of tocolytic agent

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 in the Nifedipine arm.

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	16	22
Count of Participants [Participants]	12 60%	18 81.8%

3. Secondary Outcome

Title	Number of Days From First Dose of Tocolytic Agent to Delivery
Description	Length of time from tocolytic initiation to the time of delivery
Time Frame	from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 in the Nifedipine arm.

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	16	22
Median (Inter-Quartile Range) [days]	24.8	42.6

4. Secondary Outcome

Title	Neonatal Birthweight
Time Frame	at the time of birth

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 1 neonate in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	22
Median (Inter-Quartile Range) [grams]	1870.0	2571.0

5. Secondary Outcome

Title	Neonatal Sex
Time Frame	at the time of birth

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	23
Female	6 30%	9 40.9%
Male	16 80%	14 63.6%

6. Secondary Outcome

Title	Number of Neonates Who Were Admitted to the Neonatal Intensive Care Unit (NICU)
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 1 neonate in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	22
Count of Participants [Participants]	16 80%	13 59.1%

7. Secondary Outcome

Title	Neonatal Length of Stay in NICU
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 10 neonates in the Nifedipine arm and 10 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	16	13
Median (Inter-Quartile Range) [days]	36.3	25.3

8. Secondary Outcome

Title	Neonatal Length of Hospital Stay
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 1 neonate in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	22
Median (Inter-Quartile Range) [days]	31.8	10.9

9. Secondary Outcome

Title	Number of Neonatal Deaths
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	21
Count of Participants [Participants]	1 5%	1 4.5%

10. Secondary Outcome

Title	Number of Neonates With Intraventricular Hemorrhage Diagnosed Using Cranial Ultrasonography
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	21
Count of Participants [Participants]	3 15%	2 9.1%

11. Secondary Outcome

Title	Number of Neonates With Necrotizing Enterocolitis
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	21
Count of Participants [Participants]	2 10%	0 0%

12. Secondary Outcome

Title	Number of Neonates With Culture-positive Sepsis
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	21
Count of Participants [Participants]	3 15%	3 13.6%

13. Secondary Outcome

Title	Number of Neonates With Seizures
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	21
Count of Participants [Participants]	0 0%	1 4.5%

14. Secondary Outcome

Title	Number of Neonates Who Needed Mechanical Ventilation
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	22	21
Count of Participants [Participants]	4 20%	3 13.6%

15. Secondary Outcome

Title	Neonatal Duration of Ventilator Use
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 22 neonates in the Nifedipine arm and 20 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	4	3
Median (Inter-Quartile Range) [hours]	32.5	186.0

16. Secondary Outcome

Title	Number of Neonates Who Received Continuous Positive Airway Pressure (CPAP)
Time Frame	from birth until hospital discharge or day 120 of life (whichever occurs first)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 5 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.)

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	21	21
Count of Participants [Participants]	11 55%	8 36.4%

17. Secondary Outcome

Title	Number of Maternal Participants Who Delivered by Cesarean Delivery
Time Frame	at the the time of birth

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 in the Nifedipine arm.

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	16	22
Count of Participants [Participants]	5 25%	5 22.7%

18. Secondary Outcome

Title	Number of Maternal Participants Who Had Clinical Chorioamnionitis
Time Frame	from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 in the Nifedipine arm and 1 in the Nifedipine plus Indomethacin arm.

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	16	21
Count of Participants [Participants]	1 5%	0 0%

19. Secondary Outcome

Title	Number of Maternal Participants Who Had Preterm Premature Rupture of Membranes (PPROM)
Time Frame	from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure were not collected for 4 in the Nifedipine arm and 1 in the Nifedipine plus Indomethacin arm.

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	16	21
Count of Participants [Participants]	2 10%	2 9.1%

20. Secondary Outcome

Title	Number of Maternal Participants Who Had Preeclampsia
Time Frame	from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	1 5%	2 9.1%

21. Secondary Outcome

Title	Number of Maternal Participants Who Needed Blood Transfusion
Time Frame	from time of birth to time of discharge from hospital (about 2-3 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	1 5%	1 4.5%

22. Secondary Outcome

Title	Number of Maternal Participants With Headache
Time Frame	from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	0 0%	1 4.5%

23. Secondary Outcome

Title	Number of Maternal Participants With Nausea
Time Frame	from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	1 5%	0 0%

24. Secondary Outcome

Title	Number of Maternal Participants With Vomiting
Time Frame	from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	0 0%	0 0%

25. Secondary Outcome

Title	Number of Maternal Participants With Acid Reflux
Time Frame	from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	1 5%	1 4.5%

26. Secondary Outcome

Title	Number of Maternal Participants With Hypotension
Time Frame	from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	1 5%	1 4.5%

27. Secondary Outcome

Title	Number of Maternal Participants With Tachycardia
Time Frame	from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	1 5%	1 4.5%

28. Secondary Outcome

Title	Number of Maternal Participants With Syncope
Time Frame	from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nifedipine	Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.	Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
Measure Participants	20	22
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	Maternal participants: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) Neonates: from birth until hospital discharge or day 120 of life (whichever occurs first)
Adverse Event Reporting Description	Adverse Events are reported for 20 maternal participants and 26 neonates in the Nifedipine arm (6 mothers in the Nifedipine arm had twins) and are reported for 22 maternal participants and 23 neonates in the Nifedipine Plus Indomethacin arm (1 mother in the Nifedipine Plus Indomethacin arm had twins). The 2 deaths were neonatal deaths (there were no maternal deaths).
Arm/Group Title	Nifedipine		Nifedipine Plus Indomethacin
Arm/Group Description	Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours.		Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
All Cause Mortality
	Nifedipine		Nifedipine Plus Indomethacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/46 (2.2%)		1/45 (2.2%)
Serious Adverse Events
	Nifedipine		Nifedipine Plus Indomethacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/46 (52.2%)		38/45 (84.4%)
Eye disorders
Retinopathy of prematurity (neonatal)	4/26 (15.4%)	4	1/23 (4.3%)	1
General disorders
Death (neonatal)	1/26 (3.8%)	1	1/23 (4.3%)	1
Admission to NICU (neonatal)	16/26 (61.5%)	16	13/23 (56.5%)	13
Received Blood Transfusion (maternal)	1/20 (5%)	1	1/22 (4.5%)	1
Infections and infestations
Necrotizing Enterocolitis (neonatal)	2/26 (7.7%)	2	0/23 (0%)	0
Culture-Positive Sepsis (neonatal)	3/26 (11.5%)	3	3/23 (13%)	3
Nervous system disorders
Seizures (neonatal)	0/26 (0%)	0	1/23 (4.3%)	1
Respiratory, thoracic and mediastinal disorders
Received Mechanical Ventilation (neonatal)	4/26 (15.4%)	4	3/23 (13%)	3
Received Continuous Positive Airway Pressure (CPAP) (neonatal)	11/26 (42.3%)	11	8/23 (34.8%)	8
Respiratory distress syndrome (RDS) (neonatal)	10/26 (38.5%)	10	5/23 (21.7%)	5
Vascular disorders
Intraventricular Hemorrhage (neonatal)	3/26 (11.5%)	3	2/23 (8.7%)	2
Other (Not Including Serious) Adverse Events
	Nifedipine		Nifedipine Plus Indomethacin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/46 (8.7%)		4/45 (8.9%)
Cardiac disorders
Tachycardia (maternal)	1/20 (5%)	1	1/22 (4.5%)	1
Gastrointestinal disorders
Acid Reflux (maternal)	1/20 (5%)	1	1/22 (4.5%)	1
General disorders
Headache (maternal)	0/20 (0%)	0	1/22 (4.5%)	1
Nausea (maternal)	1/20 (5%)	1	0/22 (0%)	0
Infections and infestations
Clinical Chorioamnionitis (maternal)	1/20 (5%)	1	0/22 (0%)	0
Pregnancy, puerperium and perinatal conditions
Preterm Premature Rupture of Membranes (PPROM) (maternal)	2/20 (10%)	2	2/22 (9.1%)	2
Preeclampsia (maternal)	1/20 (5%)	1	2/22 (9.1%)	2
Vascular disorders
Hypotension (maternal)	1/20 (5%)	1	1/22 (4.5%)	1

Limitations/Caveats

Small sample size

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.