Vaginal Indomethacin for Preterm Labor (TOCOMED)
Primary Purpose
Obstetric Labor, Premature
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Indomethacin
Nifedipine
Sponsored by
About this trial
This is an interventional treatment trial for Obstetric Labor, Premature focused on measuring preterm labor, tocolysis, prematurity
Eligibility 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:
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Indomethacin group
Nifedipine group
Arm Description
Group of patients receiving Indomethacin for preterm labor treatment.
Group of patients receiving Nifedipine for preterm labor treatment.
Outcomes
Primary Outcome Measures
Time to delivery
The time from administration of intervention do delivery
Gestational age
Days from last menstrual period
Secondary Outcome Measures
Rate of preterm deliveries
Rate of deliveries under 37+0/7 weeks of gestation
Rate of remote from term deliveries
Rate of deliveries under 34+0/7 weeks of gestation
Rate of extreme preterm deliveries
Rate of deliveries under 28+0/7 weeks of gestation
neonatal immediate outcomes
Neonatal Apgar scores
Neonatal immediate outcome
Neonatal umbilical cord pH levels
Neonatal birth weight
birth wight as recorded in chart in grams
Neonatal outcomes
neonatal intensive care unit administration rate
Full Information
NCT ID
NCT04404686
First Posted
May 7, 2020
Last Updated
August 10, 2020
Sponsor
Hadassah Medical Organization
Collaborators
Sheba Medical Center, Soroka University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04404686
Brief Title
Vaginal Indomethacin for Preterm Labor
Acronym
TOCOMED
Official Title
Vaginal Indomethacin Versus Oral Nifedipine for Preterm Labor; a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2020 (Anticipated)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
April 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hadassah Medical Organization
Collaborators
Sheba Medical Center, Soroka University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstetric Labor, Premature
Keywords
preterm labor, tocolysis, prematurity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Masking Description
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
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Indomethacin group
Arm Type
Experimental
Arm Description
Group of patients receiving Indomethacin for preterm labor treatment.
Arm Title
Nifedipine group
Arm Type
Active Comparator
Arm Description
Group of patients receiving Nifedipine for preterm labor treatment.
Intervention Type
Drug
Intervention Name(s)
Indomethacin
Other Intervention Name(s)
Indomed
Intervention Description
Per vagina administration of 100 mg followed by a second 100 mg dosage the following day
Intervention Type
Drug
Intervention Name(s)
Nifedipine
Other Intervention Name(s)
Pressolat
Intervention Description
Per os administration according to current protocol of 20mg each 20 minutes for 1 hour followed by 20 mg q8 for 48 hours.
Primary Outcome Measure Information:
Title
Time to delivery
Description
The time from administration of intervention do delivery
Time Frame
through study completion, approximately 1 year
Title
Gestational age
Description
Days from last menstrual period
Time Frame
through study completion, approximately 1 year
Secondary Outcome Measure Information:
Title
Rate of preterm deliveries
Description
Rate of deliveries under 37+0/7 weeks of gestation
Time Frame
through study completion, approximately 1 year
Title
Rate of remote from term deliveries
Description
Rate of deliveries under 34+0/7 weeks of gestation
Time Frame
through study completion, approximately 1 year
Title
Rate of extreme preterm deliveries
Description
Rate of deliveries under 28+0/7 weeks of gestation
Time Frame
through study completion, approximately 1 year
Title
neonatal immediate outcomes
Description
Neonatal Apgar scores
Time Frame
through study completion, approximately 1 year
Title
Neonatal immediate outcome
Description
Neonatal umbilical cord pH levels
Time Frame
through study completion, approximately 1 year
Title
Neonatal birth weight
Description
birth wight as recorded in chart in grams
Time Frame
through study completion, approximately 1 year
Title
Neonatal outcomes
Description
neonatal intensive care unit administration rate
Time Frame
through study completion, approximately 1 year
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Pregnant women
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hila Hochler, MD
Phone
00 972 52 300 3722
Email
hilahochler@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hadas Lemberg, PhD
Phone
00 972 2 6777572
Email
lhadas@hadassah.org.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hila Hochler, MD
Organizational Affiliation
Hadassah Medical Organization
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
7369252
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. doi: 10.1016/0002-9378(80)90629-8.
Results Reference
background
PubMed Identifier
6374098
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. doi: 10.1515/jpme.1984.12.1.25.
Results Reference
background
PubMed Identifier
2014850
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. doi: 10.1016/0002-9378(91)90569-d.
Results Reference
background
PubMed Identifier
19300321
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):585-594. doi: 10.1097/AOG.0b013e318199924a.
Results Reference
background
PubMed Identifier
8665768
Citation
O'Brien WF. The role of prostaglandins in labor and delivery. Clin Perinatol. 1995 Dec;22(4):973-84.
Results Reference
background
PubMed Identifier
2496208
Citation
Bry K, Hallman M. Prostaglandins, inflammation, and preterm labor. J Perinatol. 1989 Mar;9(1):60-5.
Results Reference
background
PubMed Identifier
10725476
Citation
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.
Results Reference
background
PubMed Identifier
24901312
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;2014(6):CD002255. doi: 10.1002/14651858.CD002255.pub2.
Results Reference
background
PubMed Identifier
26042617
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;2015(6):CD001992. doi: 10.1002/14651858.CD001992.pub3.
Results Reference
background
PubMed Identifier
21457979
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.
Results Reference
background
PubMed Identifier
22873356
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.
Results Reference
background
PubMed Identifier
24090282
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.
Results Reference
background
PubMed Identifier
35947046
Citation
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.
Results Reference
derived
Learn more about this trial
Vaginal Indomethacin for Preterm Labor
We'll reach out to this number within 24 hrs