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

Phase 3

Completed

• Conditions: Intraventricular Hemorrhage (IVH); Bleeding in the Brain; Prematurity; Very Low Birth Weight Infants
• Interventions: Drug: indomethacin; Drug: placebo

• Registration Number: NCT00033917
• Lead Sponsor: Yale University

Brief Summary

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

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.

Study Timeline

• Study Start: 1989-09
• Study First Submitted: 2002-04-12
• Study First Submitted QC: 2002-04-12
• Study First Posted: 2002-04-15
• Primary Completion: 2012-03
• Study Completion: 2012-03
• Results First Submitted: 2013-01-08
• Status Verified: 2013-02
• Results First Submitted QC: 2013-02-20
• Last Update Submitted: 2013-02-20
• Results First Posted: 2013-03-28
• Last Update Posted: 2013-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 630

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	indomethacin	indomethacin
2	placebo	placebo

Primary Outcome Measures

Name	Time	Method
IVH at 5 Postnatal Days	at 5 days	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

Name	Time	Method
Language Outcome	at 8 years	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.

Trial Locations

Locations (3)

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Maine Medical Center; 🇺🇸 Portland, Maine, United States

Brown University School of Medicine; 🇺🇸 Providence, Rhode Island, United States