Clinical trial NCT01869361: Indomethacin for Tocolysis of Preterm Labor
Official title: Randomized, Placebo Controlled Trial of Indomethacin for Tocolysis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Preterm Labor
Keywords: preterm labor
tocolysis
indomethacin
Lead sponsor: MetroHealth Medical Center
Sponsor class: OTHER
First posted: 2013-06-05
Enrollment: 0
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: delivery within 48 hours
timeFrame: 48 hours after enrollment
Secondary outcomes:
measure: delivery within 7 days
timeFrame: 7 days after enrollment
measure: delivery before 37 weeks
timeFrame: participants will be followed for the duration of pregnancy through their postpartum period, an expected time of up to 20 weeks
measure: Maternal and Fetal Complications
timeFrame: 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
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
Study officials:
affiliation: MetroHealth Medical Center
name: Kelly S Gibson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MetroHealth Medical Center
name: Brian Mercer, MD
role: STUDY_CHAIR
References:
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.
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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.
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.
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.
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.
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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.
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.