Vaginal Indomethacin for Preterm Labor

Obstetric Labor, Premature Clinical Trial

— TOCOMED  

Official title:

Vaginal Indomethacin Versus Oral Nifedipine for Preterm Labor; a Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04404686
• Other study ID #: TOCOMED-HMO-CTIL
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: October 2020
• Est. completion date: April 2025

Study information

• Verified date: August 2020
• Source: Hadassah Medical Organization
• Contact: Hila Hochler, MD
• Phone: 00 972 52 300 3722
• Email: hilahochler[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Indometacin is a cyclooxygenase agent from the NSAID family that has been used to treat preterm contractions since the 70's by preventing the synthesis of prostaglandins. It has been shown to be significantly more effective than placebo and postpone labor for 7-10 days, prolong pregnancies above 37 weeks of gestation and reduce numbers of small for gestational age neonates.

Nifedipine is a calcium channel blocker agent that has been shown to reduce rates of labor within 48 hours from treatment.

Previous studies comparing rectal Indometacin to oral nifedipine were inconclusive.

Prostaglandins are synthesized in the uterus and the uterine cervix and therefore local administration of Indometacin may be more effective than other forms of administration, as been shown in a previous study.

In this study we aim to compare vaginal Indometacin administration to a commonly used tocolytic agent, nifedipine.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: April 2025
• Est. primary completion date: April 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 60 Years

Eligibility

Inclusion Criteria:

• Singe fetus

• Gestational age between 24+0/7 and 31+6/7

• At least one uterine contraction in ten minutes for at least 20 minutes upon tocography admission

• Cervical parameters: 1 cm dilation or more or 80% cervical effacement or cervical length 20mm or less

Exclusion Criteria:

• Rupture of membranes

• Vaginal bleeding

• Cervical dilation =5cm

• Known fetal malformations

• Fetal heart rate abnormalities

• Suspected placental abruption of adherent placental syndrome

• Known sensitivity to one of the drugs used in the study (Indometacin and nifedipine)

• Maternal hypotension and known aortic or mitral stenosis

• Presence of cervical cerclage

• Previous administration of tocolytic drugs in current pregnancy

Related Conditions & MeSH terms

• Obstetric Labor, Premature

Intervention

Drug:
• Indomethacin
Per vagina administration of 100 mg followed by a second 100 mg dosage the following day
• Nifedipine
Per os administration according to current protocol of 20mg each 20 minutes for 1 hour followed by 20 mg q8 for 48 hours.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Hadassah Medical Organization	Sheba Medical Center, Soroka University Medical Center

References & Publications (12)

Abramov Y, Nadjari M, Weinstein D, Ben-Shachar I, Plotkin V, Ezra Y. Indomethacin for preterm labor: a randomized comparison of vaginal and rectal-oral routes. Obstet Gynecol. 2000 Apr;95(4):482-6. — View Citation

Besinger RE, Niebyl JR, Keyes WG, Johnson TR. Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor. Am J Obstet Gynecol. 1991 Apr;164(4):981-6; discussion 986-8. — View Citation

Bry K, Hallman M. Prostaglandins, inflammation, and preterm labor. J Perinatol. 1989 Mar;9(1):60-5. Review. — View Citation

Flenady V, Wojcieszek AM, Papatsonis DN, Stock OM, Murray L, Jardine LA, Carbonne B. Calcium channel blockers for inhibiting preterm labour and birth. Cochrane Database Syst Rev. 2014 Jun 5;(6):CD002255. doi: 10.1002/14651858.CD002255.pub2. Review. — View Citation

Haas DM, Imperiale TF, Kirkpatrick PR, Klein RW, Zollinger TW, Golichowski AM. Tocolytic therapy: a meta-analysis and decision analysis. Obstet Gynecol. 2009 Mar;113(3):585-94. doi: 10.1097/AOG.0b013e318199924a. — View Citation

Kashanian M, Bahasadri S, Zolali B. Comparison of the efficacy and adverse effects of nifedipine and indomethacin for the treatment of preterm labor. Int J Gynaecol Obstet. 2011 Jun;113(3):192-5. doi: 10.1016/j.ijgo.2010.12.019. Epub 2011 Apr 1. — View Citation

Klauser CK, Briery CM, Keiser SD, Martin RW, Kosek MA, Morrison JC. Effect of antenatal tocolysis on neonatal outcomes. J Matern Fetal Neonatal Med. 2012 Dec;25(12):2778-81. doi: 10.3109/14767058.2012.714819. Epub 2012 Aug 20. — View Citation

Klauser CK, Briery CM, Martin RW, Langston L, Magann EF, Morrison JC. A comparison of three tocolytics for preterm labor: a randomized clinical trial. J Matern Fetal Neonatal Med. 2014 May;27(8):801-6. doi: 10.3109/14767058.2013.847416. Epub 2013 Oct 11. — 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

O'Brien WF. The role of prostaglandins in labor and delivery. Clin Perinatol. 1995 Dec;22(4):973-84. Review. — View Citation

Reinebrant HE, Pileggi-Castro C, Romero CL, Dos Santos RA, Kumar S, Souza JP, Flenady V. Cyclo-oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database Syst Rev. 2015 Jun 5;(6):CD001992. doi: 10.1002/14651858.CD001992.pub3. Review. — 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	Time to delivery	The time from administration of intervention do delivery	through study completion, approximately 1 year
Primary	Gestational age	Days from last menstrual period	through study completion, approximately 1 year
Secondary	Rate of preterm deliveries	Rate of deliveries under 37+0/7 weeks of gestation	through study completion, approximately 1 year
Secondary	Rate of remote from term deliveries	Rate of deliveries under 34+0/7 weeks of gestation	through study completion, approximately 1 year
Secondary	Rate of extreme preterm deliveries	Rate of deliveries under 28+0/7 weeks of gestation	through study completion, approximately 1 year
Secondary	neonatal immediate outcomes	Neonatal Apgar scores	through study completion, approximately 1 year
Secondary	Neonatal immediate outcome	Neonatal umbilical cord pH levels	through study completion, approximately 1 year
Secondary	Neonatal birth weight	birth wight as recorded in chart in grams	through study completion, approximately 1 year
Secondary	Neonatal outcomes	neonatal intensive care unit administration rate	through study completion, approximately 1 year