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

NCT ID: NCT00033917

Last Updated: 2013-03-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

630 participants

Study Classification

INTERVENTIONAL

Study Start Date

1989-09-30

Study Completion Date

2012-03-31

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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

indomethacin

Group Type ACTIVE_COMPARATOR

indomethacin

Intervention Type DRUG

an anti-inflammatory drug

2

placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

saline

Interventions

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indomethacin

an anti-inflammatory drug

Intervention Type DRUG

placebo

saline

Intervention Type DRUG

Eligibility Criteria

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Inclusion 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
Maximum Eligible Age

6 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Yale University

OTHER

Sponsor Role lead

Responsible Party

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Laura R. Ment

Professor Pediatrics and Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Laura R. Ment, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Pediatrics, Yale University School of Medicine

Locations

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Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

Maine Medical Center

Portland, Maine, United States

Site Status

Brown University School of Medicine

Providence, Rhode Island, United States

Site Status

Countries

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United States

References

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Ment LR, Oh W, Ehrenkranz RA, Philip AG, Vohr B, Allan W, Duncan CC, Scott DT, Taylor KJ, Katz KH, et al. Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial. Pediatrics. 1994 Apr;93(4):543-50.

Reference Type BACKGROUND
PMID: 8134206 (View on PubMed)

Ment LR, Oh W, Ehrenkranz RA, Phillip AG, Vohr B, Allan W, Makuch RW, Taylor KJ, Schneider KC, Katz KH, et al. Low-dose indomethacin therapy and extension of intraventricular hemorrhage: a multicenter randomized trial. J Pediatr. 1994 Jun;124(6):951-5. doi: 10.1016/s0022-3476(05)83191-9.

Reference Type BACKGROUND
PMID: 8201485 (View on PubMed)

Ment LR, Vohr B, Oh W, Scott DT, Allan WC, Westerveld M, Duncan CC, Ehrenkranz RA, Katz KH, Schneider KC, Makuch RW. Neurodevelopmental outcome at 36 months' corrected age of preterm infants in the Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial. Pediatrics. 1996 Oct;98(4 Pt 1):714-8.

Reference Type BACKGROUND
PMID: 8885951 (View on PubMed)

Ment LR, Westerveld M, Makuch R, Vohr B, Allan WC. Cognitive outcome at 4 1/2 years of very low birth weight infants enrolled in the multicenter indomethacin intraventricular hemorrhage prevention trial. Pediatrics. 1998 Jul;102(1 Pt 1):159-60. doi: 10.1542/peds.102.1.159. No abstract available.

Reference Type BACKGROUND
PMID: 9714645 (View on PubMed)

Ment LR, Vohr B, Allan W, Westerveld M, Sparrow SS, Schneider KC, Katz KH, Duncan CC, Makuch RW. Outcome of children in the indomethacin intraventricular hemorrhage prevention trial. Pediatrics. 2000 Mar;105(3 Pt 1):485-91. doi: 10.1542/peds.105.3.485.

Reference Type BACKGROUND
PMID: 10699097 (View on PubMed)

Peterson BS, Vohr B, Staib LH, Cannistraci CJ, Dolberg A, Schneider KC, Katz KH, Westerveld M, Sparrow S, Anderson AW, Duncan CC, Makuch RW, Gore JC, Ment LR. Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. JAMA. 2000 Oct 18;284(15):1939-47. doi: 10.1001/jama.284.15.1939.

Reference Type BACKGROUND
PMID: 11035890 (View on PubMed)

Ment LR, Vohr B, Allan W, Katz KH, Schneider KC, Westerveld M, Duncan CC, Makuch RW. Change in cognitive function over time in very low-birth-weight infants. JAMA. 2003 Feb 12;289(6):705-11. doi: 10.1001/jama.289.6.705.

Reference Type BACKGROUND
PMID: 12585948 (View on PubMed)

Ment LR, Peterson BS, Meltzer JA, Vohr B, Allan W, Katz KH, Lacadie C, Schneider KC, Duncan CC, Makuch RW, Constable RT. A functional magnetic resonance imaging study of the long-term influences of early indomethacin exposure on language processing in the brains of prematurely born children. Pediatrics. 2006 Sep;118(3):961-70. doi: 10.1542/peds.2005-2870.

Reference Type BACKGROUND
PMID: 16950986 (View on PubMed)

Ment LR, Kesler S, Vohr B, Katz KH, Baumgartner H, Schneider KC, Delancy S, Silbereis J, Duncan CC, Constable RT, Makuch RW, Reiss AL. Longitudinal brain volume changes in preterm and term control subjects during late childhood and adolescence. Pediatrics. 2009 Feb;123(2):503-11. doi: 10.1542/peds.2008-0025.

Reference Type BACKGROUND
PMID: 19171615 (View on PubMed)

Gozzo Y, Vohr B, Lacadie C, Hampson M, Katz KH, Maller-Kesselman J, Schneider KC, Peterson BS, Rajeevan N, Makuch RW, Constable RT, Ment LR. Alterations in neural connectivity in preterm children at school age. Neuroimage. 2009 Nov 1;48(2):458-63. doi: 10.1016/j.neuroimage.2009.06.046. Epub 2009 Jun 25.

Reference Type BACKGROUND
PMID: 19560547 (View on PubMed)

Luu TM, Vohr BR, Schneider KC, Katz KH, Tucker R, Allan WC, Ment LR. Trajectories of receptive language development from 3 to 12 years of age for very preterm children. Pediatrics. 2009 Jul;124(1):333-41. doi: 10.1542/peds.2008-2587.

Reference Type BACKGROUND
PMID: 19564317 (View on PubMed)

Myers EH, Hampson M, Vohr B, Lacadie C, Frost SJ, Pugh KR, Katz KH, Schneider KC, Makuch RW, Constable RT, Ment LR. Functional connectivity to a right hemisphere language center in prematurely born adolescents. Neuroimage. 2010 Jul 15;51(4):1445-52. doi: 10.1016/j.neuroimage.2010.03.049. Epub 2010 Mar 25.

Reference Type BACKGROUND
PMID: 20347043 (View on PubMed)

Mullen KM, Vohr BR, Katz KH, Schneider KC, Lacadie C, Hampson M, Makuch RW, Reiss AL, Constable RT, Ment LR. Preterm birth results in alterations in neural connectivity at age 16 years. Neuroimage. 2011 Feb 14;54(4):2563-70. doi: 10.1016/j.neuroimage.2010.11.019. Epub 2010 Nov 10.

Reference Type BACKGROUND
PMID: 21073965 (View on PubMed)

Luu TM, Vohr BR, Allan W, Schneider KC, Ment LR. Evidence for catch-up in cognition and receptive vocabulary among adolescents born very preterm. Pediatrics. 2011 Aug;128(2):313-22. doi: 10.1542/peds.2010-2655. Epub 2011 Jul 18.

Reference Type BACKGROUND
PMID: 21768322 (View on PubMed)

Constable RT, Vohr BR, Scheinost D, Benjamin JR, Fulbright RK, Lacadie C, Schneider KC, Katz KH, Zhang H, Papademetris X, Ment LR. A left cerebellar pathway mediates language in prematurely-born young adults. Neuroimage. 2013 Jan 1;64:371-8. doi: 10.1016/j.neuroimage.2012.09.008. Epub 2012 Sep 12.

Reference Type BACKGROUND
PMID: 22982585 (View on PubMed)

Reiss AL, Kesler SR, Vohr B, Duncan CC, Katz KH, Pajot S, Schneider KC, Makuch RW, Ment LR. Sex differences in cerebral volumes of 8-year-olds born preterm. J Pediatr. 2004 Aug;145(2):242-9. doi: 10.1016/j.jpeds.2004.04.031.

Reference Type BACKGROUND
PMID: 15289777 (View on PubMed)

Other Identifiers

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R01NS027116

Identifier Type: NIH

Identifier Source: org_study_id

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