Indomethacin for Tocolysis of Preterm Labor

NCT ID: NCT01869361

Last Updated: 2021-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

EARLY_PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-01

Study Completion Date

2021-11-23

Brief Summary

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Indomethacin for tocolysis for 48 hours vs placebo

Detailed Description

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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.

Conditions

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Preterm Labor

Keywords

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preterm labor tocolysis indomethacin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Control drug

Indomethacin

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.

Group Type ACTIVE_COMPARATOR

Indomethacin

Intervention Type DRUG

Study drug

Interventions

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Indomethacin

Study drug

Intervention Type DRUG

Placebo

Control drug

Intervention Type DRUG

Other Intervention Names

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Indocin

Eligibility Criteria

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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)
Minimum Eligible Age

16 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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MetroHealth Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Kelly S Gibson

Maternal Fetal Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kelly S Gibson, MD

Role: PRINCIPAL_INVESTIGATOR

MetroHealth Medical Center

Brian Mercer, MD

Role: STUDY_CHAIR

MetroHealth Medical Center

Locations

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MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 22617615 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23048010 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17904969 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22370109 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6374098 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7369252 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10430197 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17980183 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21690109 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15994634 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17053778 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1986601 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35947046 (View on PubMed)

Other Identifiers

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IRB13-00533

Identifier Type: -

Identifier Source: org_study_id