NCT04404686

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2020

Typical duration for phase_2

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 7, 2020

Completed
20 days until next milestone

First Posted

Study publicly available on registry

May 27, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

October 1, 2020

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2024

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2025

Completed
Last Updated

August 11, 2020

Status Verified

August 1, 2020

Enrollment Period

3.5 years

First QC Date

May 7, 2020

Last Update Submit

August 10, 2020

Conditions

Obstetric Labor, Premature

Keywords

preterm labortocolysisprematurity

Outcome Measures

Primary Outcomes (2)

  • Time to delivery

    The time from administration of intervention do delivery

    through study completion, approximately 1 year

  • Gestational age

    Days from last menstrual period

    through study completion, approximately 1 year

Secondary Outcomes (7)

  • Rate of preterm deliveries

    through study completion, approximately 1 year

  • Rate of remote from term deliveries

    through study completion, approximately 1 year

  • Rate of extreme preterm deliveries

    through study completion, approximately 1 year

  • neonatal immediate outcomes

    through study completion, approximately 1 year

  • Neonatal immediate outcome

    through study completion, approximately 1 year

  • +2 more secondary outcomes

Study Arms (2)

Indomethacin group

EXPERIMENTAL

Group of patients receiving Indomethacin for preterm labor treatment.

Drug: Indomethacin

Nifedipine group

ACTIVE COMPARATOR

Group of patients receiving Nifedipine for preterm labor treatment.

Drug: Nifedipine

Interventions

IndomethacinDRUG

Per vagina administration of 100 mg followed by a second 100 mg dosage the following day

Also known as: Indomed
Indomethacin group
NifedipineDRUG

Per os administration according to current protocol of 20mg each 20 minutes for 1 hour followed by 20 mg q8 for 48 hours.

Also known as: Pressolat
Nifedipine group

Eligibility Criteria

Age16 Years - 60 Years
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsPregnant women
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (13)

  • 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: 7369252BACKGROUND

  • 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: 6374098BACKGROUND

  • 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. doi: 10.1016/0002-9378(91)90569-d.

    PMID: 2014850BACKGROUND

  • 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.

    PMID: 19300321BACKGROUND

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

    PMID: 8665768BACKGROUND

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

    PMID: 2496208BACKGROUND

  • 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. doi: 10.1016/s0029-7844(99)00578-5.

    PMID: 10725476BACKGROUND

  • 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;2014(6):CD002255. doi: 10.1002/14651858.CD002255.pub2.

    PMID: 24901312BACKGROUND

  • 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;2015(6):CD001992. doi: 10.1002/14651858.CD001992.pub3.

    PMID: 26042617BACKGROUND

  • 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.

    PMID: 21457979BACKGROUND

  • 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.

    PMID: 22873356BACKGROUND

  • 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.

    PMID: 24090282BACKGROUND

  • 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: 35947046DERIVED

MeSH Terms

Conditions

Obstetric Labor, PrematurePremature Birth

Interventions

IndomethacinNifedipine

Condition Hierarchy (Ancestors)

Obstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Intervention Hierarchy (Ancestors)

IndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDihydropyridinesPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Hila Hochler, MD

    Hadassah Medical Organization

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Hila Hochler, MD

CONTACT

00 972 52 300 3722hilahochler@gmail.com

Hadas Lemberg, PhD

CONTACT

00 972 2 6777572lhadas@hadassah.org.il

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Caregivers will receive a closed envelope with the drug to be used. since the routes of administration are different, from that point on the caregiver and patient will be aware of chosen drug
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

May 7, 2020

First Posted

May 27, 2020

Study Start

October 1, 2020

Primary Completion

April 1, 2024

Study Completion

April 1, 2025

Last Updated

August 11, 2020

Record last verified: 2020-08

Data Sharing

IPD Sharing
Will not share