Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Laura R. Ment, Yale University
ClinicalTrials.gov Identifier:
NCT00033917
First received: April 12, 2002
Last updated: February 20, 2013
Last verified: February 2013
  Purpose

The purpose of this multicenter trial is to determine if indomethacin prevents bleeding in the brain of very low birth weight preterm infants.


Condition Intervention Phase
Intraventricular Hemorrhage (IVH)
Bleeding in the Brain
Prematurity
Very Low Birth Weight Infants
Drug: indomethacin
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Randomized Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • IVH at 5 Postnatal Days [ Time Frame: at 5 days ] [ Designated as safety issue: No ]
    Cranial ultrasounds were performed daily for the first 5 postnatal days; the main outcome measure was intraaventricular hemorrhage (IVH) at 5 days of age


Secondary Outcome Measures:
  • Language Outcome [ Time Frame: at 8 years ] [ Designated as safety issue: No ]

    Peabody Picture Vocabulary Test (PPVT) This is a semantic language test. The mean value is 100; standard deviation is 16 points. A higher score means better language; a lower score means poorer language.

    There are no subscales to the PPVT. The measurement unit is points on a scale. A score < 70 indicates severely abnormal language function.



Enrollment: 630
Study Start Date: September 1989
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
indomethacin
Drug: indomethacin
an anti-inflammatory drug
Placebo Comparator: 2
placebo
Drug: placebo
saline

Detailed Description:

Intraventricular hemorrhage (IVH) or bleeding in the brain remains a major problem of preterm infants. This randomized, placebo-controlled multicenter trial enrolled 505 infants of 600 to 1250g birth weight to determine if indomethacin lowers the incidence of IVH, and 125 term infant controls. During this longitudinal trial, follow-up assessments have been performed at the ages of 3, 4 1/2, 6, 8, 12 and 16 years. The initial results at age 3 years revealed no advantages to the indomethacin group over and above the decreases in IVH, however, the results did show a significant increase in ventriculomegaly in the "placebo" group. Results at 4 1/2, 6 and 8 years of age showed beneficial effects of indomethacin on cognitive and behavioral outcomes over and above the effects on preventing IVH but not at later ages. At 12 and 16 years, no significant influence of indomethacin on cognitive outcome was noted.

Age, gender and zip-code matched control subjects were added when the preterm subjects were 8 years. Throughout all subsequent testing, term controls have higher IQ and Peabody Picture Vocabulary Scores.

Additional longitudinal volumetric, functional and diffusion tensor MR imaging studies showed differences between preterm and term control subjects at 8, 12 and 16 years of age. These were consistent with utilization of the right hemisphere and left cerebellum for language in the preterm group compared to term controls. No effects of indomethacin were seen.

The study closed on 31 March 2012.

  Eligibility

Ages Eligible for Study:   up to 6 Hours
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • Preterm infants < 1250 g birth weight
  • Admitted to participating institution < 6 hrs of age
  • No evidence for congenital malformations
  • Cranial US at 6 postnatal hours without evidence of Grades III - IV intraventricular hemorrhage
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00033917

Locations
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States
United States, Maine
Maine Medical Center
Portland, Maine, United States
United States, Rhode Island
Brown University School of Medicine
Providence, Rhode Island, United States
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Laura R. Ment, M.D. Department of Pediatrics, Yale University School of Medicine
  More Information

Publications:

Responsible Party: Laura R. Ment, Professor Pediatrics and Neurology, Yale University
ClinicalTrials.gov Identifier: NCT00033917     History of Changes
Other Study ID Numbers: R01NS27116
Study First Received: April 12, 2002
Results First Received: January 8, 2013
Last Updated: February 20, 2013
Health Authority: United States: Federal Government

Keywords provided by Yale University:
intraventricular hemorrhage (IVH)
bleeding in the brain
indomethacin
prematurity
very low birth weight infants

Additional relevant MeSH terms:
Birth Weight
Hemorrhage
Cerebral Hemorrhage
Body Weight
Signs and Symptoms
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Indomethacin
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 14, 2014