Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial - Full Text View

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:

Genetics Home Reference related topics: COL4A1-related brain small-vessel disease

MedlinePlus related topics: Birth Weight Premature Babies

Drug Information available for: Indomethacin

U.S. FDA Resources

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:

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 May 16, 2013