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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Intraventricular Hemorrhage (IVH), Bleeding in the Brain, Prematurity, Very Low Birth Weight Infants

Intervention / Treatment
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* Drug: indomethacin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 6 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>indomethacin | Drug: indomethacin<br>* an anti-inflammatory drug<br>|
| Placebo Comparator: 2<br>placebo | Drug: placebo<br>* saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IVH at 5 Postnatal 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 | at 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Language Outcome | 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. | at 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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indomethacin, intraventricular hemorrhage (IVH), bleeding in the brain, prematurity, very low birth weight infants