Indomethacin for Tocolysis of Preterm Labor

Preterm Labor Clinical Trial

Official title:

Randomized, Placebo Controlled Trial of Indomethacin for Tocolysis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01869361
• Other study ID #: IRB13-00533
• Status: Withdrawn
• Phase: Early Phase 1
• Start date: August 1, 2020
• Est. completion date: November 23, 2021

Study information

• Verified date: November 2021
• Source: MetroHealth Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Indomethacin for tocolysis for 48 hours vs placebo

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 23, 2021
• Est. primary completion date: November 23, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years to 50 Years

Eligibility

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)

Related Conditions & MeSH terms

• Obstetric Labor, Premature
• Premature Birth
• Preterm Labor

Intervention

Drug:
• Indomethacin
Study drug
• Placebo
Control drug

Locations

Country	Name	City	State
United States	MetroHealth Medical Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
MetroHealth Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. Review. — View 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. — View 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. — View 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. Epub 2006 Oct 19. — View 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. — View 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. Review. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	delivery within 48 hours	The percentage of patients remaining undelivered after 48 hours	48 hours after enrollment
Secondary	delivery within 7 days	The percentage of patients remaining undelivered after 7 days	7 days after enrollment
Secondary	delivery before 37 weeks	The percentage of patients remaining undelivered until 37 weeks gestational age	participants will be followed for the duration of pregnancy through their postpartum period, an expected time of up to 20 weeks
Secondary	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.	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