Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP) (TIPP)

June 3, 2015 updated by: NICHD Neonatal Research Network
This trial was to determine whether giving low-dose indomethacin to infants weight 500 to 999 grams (approximately 1 to 2 pounds) at birth improves their survival without cerebral palsy or developmental problems at 18 to 22 months of age.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Prophylactic indomethacin reduces patent ductus arteriosus (PDA) and intraventricular hemorrhage in very low birth weight infants. However, the effects of early indomethacin on long-term neurodevelopment remain uncertain. There is also insufficient evidence to rule out serious adverse effects, such as increases in the risk of necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). The aim of this trial was to determine if prophylactic administration of indomethacin improves survival without neurosensory impairments in extremely-low-birth-weight infants. Infants (n=1202) with birthweights 500 to 999 grams were randomized between 2 and 6 hours after birth to receive either intravenous indomethacin (0.1 mg/kg) or equal volumes of normal saline placebo, daily for 3 days. The primary outcomes at a corrected age of 18 months was a composite of death, cerebral palsy, cognitive delay, deafness, or blindness. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, cranial ultrasonographic abnormalities, nectrotizing enterocolitis and retinopathy. Infants were evaluated in follow-up at 18-22 months corrected age.

Study Type

Interventional

Enrollment (Actual)

1202

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Emory University
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State University
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University, Rainbow Babies and Children's Hospital
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Brown University, Women & Infants Hospital of Rhode Island
    • Texas
      • Dallas, Texas, United States, 75235
        • University of Texas Southwestern Medical Center at Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 hours to 6 hours (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Birth weight 500 to 999 grams;
  • Postnatal age greater than 2 hours;

Exclusion Criteria:

  • Unable to administer study drug within 6 hours of birth;
  • Structural heart disease and/or renal disease;
  • Dysmorphic features or congenital abnormalities;
  • Tocolytic therapy with indomethacin or other prostaglandin inhibitor within 72 hours prior to delivery;
  • Overt clinical bleeding from more than one site;
  • Platelet count less than 50 x 109/L;
  • Hydrops;
  • Not considered viable

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Saline solution
Drug: Placebo
0.1 mg per kilogram of body weight
Experimental: Indomethacin
Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa.
Drug: indomethacin
Indocid P.D.A., Merck Frosst, Kirkland, Que., Canada, and Merck, West Point, Pa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Death or Neurodevelopment Impairment
Time Frame: 18-22 Months Corrected Age
18-22 Months Corrected Age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patent ductus arteriosus
Time Frame: 120 Days of Life
120 Days of Life
Bronchopulmonary Dysplasia (BPD)
Time Frame: 120 Days of Life
Chronic Lung Disease (CLD)
120 Days of Life
Necrotizing enterocolitis (NEC)
Time Frame: 120 Days of Life
120 Days of Life
Intracranial abnormalities
Time Frame: 120 Days of Life
120 Days of Life
Retinopathy of Prematurity (ROP)
Time Frame: 18-22 Months Corrected Age
18-22 Months Corrected Age
Pulmonary hemorrhage
Time Frame: 120 Days of Life
120 Days of Life

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NICHD Neonatal Research Network

Collaborators

National Center for Research Resources (NCRR)
Medical Research Council of Canada

Investigators

  • Study Director: Barbara Schmidt, MD, McMaster University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 1993

Primary Completion (Actual)

March 1, 1999

Study Completion (Actual)

March 1, 2001

Study Registration Dates

First Submitted

February 1, 2001

First Submitted That Met QC Criteria

February 2, 2001

First Posted (Estimate)

February 5, 2001

Study Record Updates

Last Update Posted (Estimate)

June 8, 2015

Last Update Submitted That Met QC Criteria

June 3, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NICHD-NRN-0011
  • U10HD021364 (U.S. NIH Grant/Contract)
  • U10HD021373 (U.S. NIH Grant/Contract)
  • U10HD021385 (U.S. NIH Grant/Contract)
  • U10HD027851 (U.S. NIH Grant/Contract)
  • U10HD027880 (U.S. NIH Grant/Contract)
  • U10HD027904 (U.S. NIH Grant/Contract)
  • U10HD034216 (U.S. NIH Grant/Contract)
  • U10HD027881 (U.S. NIH Grant/Contract)
  • M01RR000070 (U.S. NIH Grant/Contract)
  • M01RR000997 (U.S. NIH Grant/Contract)
  • U10HD021397 (U.S. NIH Grant/Contract)
  • MT-13288 (Other Grant/Funding Number: Medical Research Council of Canada)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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