TOCOMED: Vaginal Indomethacin for Preterm Labor
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Indomethacin group Group of patients receiving Indomethacin for preterm labor treatment. |
Drug: Indomethacin
Per vagina administration of 100 mg followed by a second 100 mg dosage the following day
Other Names:
|
| Active Comparator: Nifedipine group Group of patients receiving Nifedipine for preterm labor treatment. |
Drug: Nifedipine
Per os administration according to current protocol of 20mg each 20 minutes for 1 hour followed by 20 mg q8 for 48 hours.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Time to delivery [through study completion, approximately 1 year]
The time from administration of intervention do delivery
- Gestational age [through study completion, approximately 1 year]
Days from last menstrual period
Secondary Outcome Measures
- Rate of preterm deliveries [through study completion, approximately 1 year]
Rate of deliveries under 37+0/7 weeks of gestation
- Rate of remote from term deliveries [through study completion, approximately 1 year]
Rate of deliveries under 34+0/7 weeks of gestation
- Rate of extreme preterm deliveries [through study completion, approximately 1 year]
Rate of deliveries under 28+0/7 weeks of gestation
- neonatal immediate outcomes [through study completion, approximately 1 year]
Neonatal Apgar scores
- Neonatal immediate outcome [through study completion, approximately 1 year]
Neonatal umbilical cord pH levels
- Neonatal birth weight [through study completion, approximately 1 year]
birth wight as recorded in chart in grams
- Neonatal outcomes [through study completion, approximately 1 year]
neonatal intensive care unit administration rate
Eligibility Criteria
Criteria
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:
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Rupture of membranes
-
Vaginal bleeding
-
Cervical dilation ≥5cm
-
Known fetal malformations
-
Fetal heart rate abnormalities
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Hadassah Medical Organization
- Sheba Medical Center
- Soroka University Medical Center
Investigators
- Principal Investigator: Hila Hochler, MD, Hadassah Medical Organization
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- Bry K, Hallman M. Prostaglandins, inflammation, and preterm labor. J Perinatol. 1989 Mar;9(1):60-5. Review.
- 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.
- 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):585-594. doi: 10.1097/AOG.0b013e318199924a.
- 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.
- 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.
- 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.
- 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.
- O'Brien WF. The role of prostaglandins in labor and delivery. Clin Perinatol. 1995 Dec;22(4):973-84. Review.
- 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.
- 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.
- TOCOMED-HMO-CTIL