Indomethacin for Tocolysis of Preterm Labor

NCT01869361 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: IRB13-00533
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Indomethacin for tocolysis for 48 hours vs placebo

Conditions

Preterm Labor

Keywords

preterm labor; tocolysis; indomethacin

Outcome Measures

Primary Outcomes (1)

• delivery within 48 hours

  The percentage of patients remaining undelivered after 48 hours

  48 hours after enrollment

Secondary Outcomes (3)

• delivery within 7 days

  7 days after enrollment

• delivery before 37 weeks

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

• Maternal and Fetal Complications

  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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Indomethacin

ACTIVE COMPARATOR

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.

Drug: Indomethacin

Interventions

Indomethacin DRUG

Study drug

Also known as: Indocin

Indomethacin

Placebo DRUG

Control drug

Placebo

Eligibility Criteria

• Age: 16 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• MetroHealth Medical Center: lead

Study Sites (1)

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Related Publications (13)

• 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.

  PMID: 22617615 BACKGROUND

• 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.

  PMID: 23048010 BACKGROUND

• 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.

  PMID: 17904969 BACKGROUND

• 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.

  PMID: 22370109 BACKGROUND

• 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.

  PMID: 6374098 BACKGROUND

• 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.

  PMID: 7369252 BACKGROUND

• 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.

  PMID: 10430197 BACKGROUND

• 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.

  PMID: 17980183 BACKGROUND

• 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.

  PMID: 21690109 BACKGROUND

• 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.

  PMID: 15994634 BACKGROUND

• 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.

  PMID: 17053778 BACKGROUND

• 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.

  PMID: 1986601 BACKGROUND

• 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.

  PMID: 35947046 DERIVED

MeSH Terms

Conditions

Obstetric Labor, Premature

Interventions

Indomethacin

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kelly S Gibson, MD

  MetroHealth Medical Center

  PRINCIPAL INVESTIGATOR

• Brian Mercer, MD

  MetroHealth Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Maternal Fetal Medicine

Study Record Dates

• First Submitted: May 29, 2013
• First Posted: June 5, 2013
• Study Start: August 1, 2020
• Primary Completion: November 23, 2021
• Study Completion: November 23, 2021
• Last Updated: December 7, 2021

Record last verified: 2021-11

Locations

US (1)