Back to results

Indomethacin for Tocolysis of Preterm Labor

Primary Purpose

Preterm Labor

Status

Withdrawn

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Indomethacin

Placebo

About this trial

This is an interventional treatment trial for Preterm Labor focused on measuring preterm labor, tocolysis, indomethacin

Eligibility Criteria

16 Years - 50 Years (Child, Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Preterm labor as defined by regular uterine contractions (at least 6/hour) with cervical change of at least 1 cm or cervical shortening on transvaginal ultrasound less than 25mm of functional length
Gestational age 23w0d to 31w6d weeks
Singleton
≥ 18 years old
Able to consent in English

Exclusion Criteria:

Major congenital anomalies associated with an increased risk of newborn death
Multiple fetal gestation (2+)
Known intrauterine fetal demise
Non-reassuring fetal status requiring delivery
Preterm premature rupture of membranes (PPROM)
Suspected or known intrauterine infection
Placenta previa
Maternal allergy or contraindication to indomethacin (peptic ulcer disease, thrombocytopenia, coagulopathy, renal or hepatic dysfunction)
Inevitable delivery (cervix ≥6cm dilated)

Sites / Locations

MetroHealth Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Indomethacin

Arm Description

The patient will be given a loading dose of 50mg placebo by mouth followed by 25mg by mouth every six hours for a total of eight doses over 48 hours.

The patient will be given a loading dose of 50mg indomethacin by mouth followed by 25mg by mouth every six hours for a total of eight doses over 48 hours.

Outcomes

Primary Outcome Measures

delivery within 48 hours

The percentage of patients remaining undelivered after 48 hours

Secondary Outcome Measures

delivery within 7 days

The percentage of patients remaining undelivered after 7 days

delivery before 37 weeks

The percentage of patients remaining undelivered until 37 weeks gestational age

Maternal and Fetal Complications

composite of maternal intolerance of the drug, birth weight, gestational age, neonatal morbidities, changes in amniotic fluid volume, fetal cardiac assessment, or premature constriction of the ductus arteriosus.

Full Information

NCT ID

NCT01869361

First Posted

May 29, 2013

Last Updated

November 23, 2021

Sponsor

MetroHealth Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01869361

Brief Title

Indomethacin for Tocolysis of Preterm Labor

Official Title

Randomized, Placebo Controlled Trial of Indomethacin for Tocolysis

Study Type

Interventional

2. Study Status

Record Verification Date

November 2021

Overall Recruitment Status

Withdrawn

Why Stopped

Due to much lower than expected numbers of eligible patients and lack of PI time, the study was not started.

Study Start Date

August 1, 2020 (Actual)

Primary Completion Date

November 23, 2021 (Actual)

Study Completion Date

November 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

MetroHealth Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Indomethacin for tocolysis for 48 hours vs placebo

Detailed Description

Background: Indomethacin is frequently used as a tocolytic, however there is currently only scant evidence to support its efficacy. Goals: To delay preterm delivery by 48 hours and to examine longer latency periods and maternal and neonatal outcomes Methods: Randomized placebo-controlled trial of indomethacin for tocolysis. Women with a singleton pregnancy between 23w0d and 31w6d in preterm labor randomly assigned to 50mg indomethacin by mouth followed by 25mg by mouth every 6hour for 48 hours or placebo. Patients receive betamethasone for fetal lung maturity, if not previously administered, and magnesium sulfate for neuroprotection. Ultrasound performed before initiation of study drug and after completion of study medication for amniotic fluid index and fetal cardiac assessment.

6. Conditions and Keywords

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

Preterm Labor

Keywords

preterm labor, tocolysis, indomethacin

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

The patient will be given a loading dose of 50mg placebo by mouth followed by 25mg by mouth every six hours for a total of eight doses over 48 hours.

Arm Title

Indomethacin

Arm Type

Active Comparator

Arm Description

The patient will be given a loading dose of 50mg indomethacin by mouth followed by 25mg by mouth every six hours for a total of eight doses over 48 hours.

Intervention Type

Drug

Intervention Name(s)

Indomethacin

Other Intervention Name(s)

Indocin

Intervention Description

Study drug

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Control drug

Primary Outcome Measure Information:

Title

delivery within 48 hours

Description

The percentage of patients remaining undelivered after 48 hours

Time Frame

48 hours after enrollment

Secondary Outcome Measure Information:

Title

delivery within 7 days

Description

The percentage of patients remaining undelivered after 7 days

Time Frame

7 days after enrollment

Title

delivery before 37 weeks

Description

The percentage of patients remaining undelivered until 37 weeks gestational age

Time Frame

participants will be followed for the duration of pregnancy through their postpartum period, an expected time of up to 20 weeks

Title

Maternal and Fetal Complications

Description

Time Frame

participants will be followed for the duration of pregnancy through their postpartum period and neonatal hospital stay, an expected time of up to 24 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Preterm labor as defined by regular uterine contractions (at least 6/hour) with cervical change of at least 1 cm or cervical shortening on transvaginal ultrasound less than 25mm of functional length Gestational age 23w0d to 31w6d weeks Singleton ≥ 18 years old Able to consent in English Exclusion Criteria: Major congenital anomalies associated with an increased risk of newborn death Multiple fetal gestation (2+) Known intrauterine fetal demise Non-reassuring fetal status requiring delivery Preterm premature rupture of membranes (PPROM) Suspected or known intrauterine infection Placenta previa Maternal allergy or contraindication to indomethacin (peptic ulcer disease, thrombocytopenia, coagulopathy, renal or hepatic dysfunction) Inevitable delivery (cervix ≥6cm dilated)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kelly S Gibson, MD

Organizational Affiliation

MetroHealth Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Brian Mercer, MD

Organizational Affiliation

MetroHealth Medical Center

Official's Role

Study Chair

Facility Information:

Facility Name

MetroHealth Medical Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44109

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22617615

Citation

American College of Obstetricians and Gynecologists; Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin no. 127: Management of preterm labor. Obstet Gynecol. 2012 Jun;119(6):1308-17. doi: 10.1097/AOG.0b013e31825af2f0.

Results Reference

background

PubMed Identifier

23048010

Citation

Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ, Welton NJ. Tocolytic therapy for preterm delivery: systematic review and network meta-analysis. BMJ. 2012 Oct 9;345:e6226. doi: 10.1136/bmj.e6226.

Results Reference

background

PubMed Identifier

17904969

Citation

Hayes E, Moroz L, Pizzi L, Baxter J. A cost decision analysis of 4 tocolytic drugs. Am J Obstet Gynecol. 2007 Oct;197(4):383.e1-6. doi: 10.1016/j.ajog.2007.06.052.

Results Reference

background

PubMed Identifier

22370109

Citation

Abramovici A, Cantu J, Jenkins SM. Tocolytic therapy for acute preterm labor. Obstet Gynecol Clin North Am. 2012 Mar;39(1):77-87. doi: 10.1016/j.ogc.2011.12.003. Epub 2012 Jan 4.

Results Reference

background

PubMed Identifier

6374098

Citation

Zuckerman H, Shalev E, Gilad G, Katzuni E. Further study of the inhibition of premature labor by indomethacin. Part II double-blind study. J Perinat Med. 1984;12(1):25-9. doi: 10.1515/jpme.1984.12.1.25.

Results Reference

background

PubMed Identifier

7369252

Citation

Niebyl JR, Blake DA, White RD, Kumor KM, Dubin NH, Robinson JC, Egner PG. The inhibition of premature labor with indomethacin. Am J Obstet Gynecol. 1980 Apr 15;136(8):1014-9. doi: 10.1016/0002-9378(80)90629-8.

Results Reference

background

PubMed Identifier

10430197

Citation

Panter KR, Hannah ME, Amankwah KS, Ohlsson A, Jefferies AL, Farine D. The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial. Br J Obstet Gynaecol. 1999 May;106(5):467-73. doi: 10.1111/j.1471-0528.1999.tb08300.x.

Results Reference

background

PubMed Identifier

17980183

Citation

Amin SB, Sinkin RA, Glantz JC. Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes. Am J Obstet Gynecol. 2007 Nov;197(5):486.e1-10. doi: 10.1016/j.ajog.2007.04.019.

Results Reference

background

PubMed Identifier

21690109

Citation

Sood BG, Lulic-Botica M, Holzhausen KA, Pruder S, Kellogg H, Salari V, Thomas R. The risk of necrotizing enterocolitis after indomethacin tocolysis. Pediatrics. 2011 Jul;128(1):e54-62. doi: 10.1542/peds.2011-0265. Epub 2011 Jun 20.

Results Reference

background

PubMed Identifier

15994634

Citation

Loe SM, Sanchez-Ramos L, Kaunitz AM. Assessing the neonatal safety of indomethacin tocolysis: a systematic review with meta-analysis. Obstet Gynecol. 2005 Jul;106(1):173-9. doi: 10.1097/01.AOG.0000168622.56478.df.

Results Reference

background

PubMed Identifier

17053778

Citation

Cordero L, Nankervis CA, Gardner D, Giannone PJ. The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants. J Perinatol. 2007 Jan;27(1):22-7. doi: 10.1038/sj.jp.7211612. Epub 2006 Oct 19.

Results Reference

background

PubMed Identifier

1986601

Citation

Eronen M, Pesonen E, Kurki T, Ylikorkala O, Hallman M. The effects of indomethacin and a beta-sympathomimetic agent on the fetal ductus arteriosus during treatment of premature labor: a randomized double-blind study. Am J Obstet Gynecol. 1991 Jan;164(1 Pt 1):141-6. doi: 10.1016/0002-9378(91)90644-7.

Results Reference

background

PubMed Identifier

35947046

Citation

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.

Results Reference

derived

Learn more about this trial

Indomethacin for Tocolysis of Preterm Labor

We'll reach out to this number within 24 hrs