Trial record 8 of 29 for:    necrotizing enterocolitis | NIH

Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)

This study has been completed.
Sponsor:
Collaborators:
Medical Research Council of Canada
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00009646
First received: February 1, 2001
Last updated: January 9, 2011
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Infant, Very Low Birth Weight
Infant, Premature
Ductus Arteriosus, Patent
Drug: indomethacin
Drug: Indomethacin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Trial of Indomethacin Prophylaxis in Preterm Infants (TIPP)

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Death or Neurodevelopment Impairment [ Time Frame: 18-22 Months Corrected Age ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Patent ductus arteriosus [ Time Frame: 120 Days of Life ] [ Designated as safety issue: Yes ]
  • Bronchopulmonary Dysplasia (BPD) [ Time Frame: 120 Days of Life ] [ Designated as safety issue: Yes ]
    Chronic Lung Disease (CLD)

  • Necrotizing enterocolitis (NEC) [ Time Frame: 120 Days of Life ] [ Designated as safety issue: Yes ]
  • Intracranial abnormalities [ Time Frame: 120 Days of Life ] [ Designated as safety issue: Yes ]
  • Retinopathy of Prematurity (ROP) [ Time Frame: 18-22 Months Corrected Age ] [ Designated as safety issue: Yes ]
  • Pulmonary hemorrhage [ Time Frame: 120 Days of Life ] [ Designated as safety issue: Yes ]

Enrollment: 1202
Study Start Date: November 1993
Study Completion Date: March 2001
Primary Completion Date: March 1999 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Indomethacin
0.1 mg per kilogram of body weight
Placebo Comparator: Placebo
Saline solution
Drug: Placebo
0.1 mg per kilogram of body weight

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.

  Eligibility

Ages Eligible for Study:   up to 6 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00009646

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48201
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, Ohio
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Rhode Island
Brown University, Women & Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Medical Research Council of Canada
Investigators
Study Director: Barbara Schmidt, MD McMaster University
Principal Investigator: David K. Stevenson, MD Stanford University
Principal Investigator: Lu-Ann Papile, MD University of New Mexico
Principal Investigator: Jon E. Tyson, MD MPH University of Texas
Principal Investigator: Waldemar A. Carlo, MD University of Alabama at Birmingham
Principal Investigator: Seetha Shankaran, MD Wayne State University
Principal Investigator: Barbara J. Stoll, MD Emory University
Principal Investigator: Avroy A. Fanaroff, MD Case Western Reserve University
Principal Investigator: Charles R. Bauer, MD University of Miami
Principal Investigator: William Oh, MD Brown University, Womens and Infants Hospital
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Barbara Schmidt/ Lead Principal Investigator, McMaster University
ClinicalTrials.gov Identifier: NCT00009646     History of Changes
Other Study ID Numbers: NICHD-NRN-0011, U10HD034216, U10HD027904, U10HD021364, U10HD027851, U10HD021397, U10HD027881, U10HD027880, U10HD021373, U10HD021385, MT-13288, M01RR000997, M01RR000070
Study First Received: February 1, 2001
Last Updated: January 9, 2011
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Chronic lung disease
Indocin
Indomethacin
Infants, very low birth weight
Intraventricular hemorrhage
Necrotizing enterocolitis
Patent ductus arteriosus
Pulmonary hemorrhage

Additional relevant MeSH terms:
Birth Weight
Ductus Arteriosus, Patent
Body Weight
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Heart Defects, Congenital
Heart Diseases
Signs and Symptoms
Indomethacin
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Gout Suppressants
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Sensory System Agents
Therapeutic Uses
Tocolytic Agents

ClinicalTrials.gov processed this record on October 23, 2014