- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00033917
Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial
Randomized Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Connecticut
-
New Haven, Connecticut, United States
- Yale University School of Medicine
-
-
Maine
-
Portland, Maine, United States
- Maine Medical Center
-
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Rhode Island
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Providence, Rhode Island, United States
- Brown University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 2
placebo
|
saline
|
Active Comparator: 1
indomethacin
|
an anti-inflammatory drug
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
IVH at 5 Postnatal Days
Time Frame: 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
|
at 5 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Language Outcome
Time Frame: 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. |
at 8 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Laura R. Ment, M.D., Department of Pediatrics, Yale University School of Medicine
Publications and helpful links
General 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. doi: 10.1016/s0022-3476(05)83191-9.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. doi: 10.1016/j.jpeds.2004.04.031.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Body Weight
- Pregnancy Complications
- Obstetric Labor Complications
- Obstetric Labor, Premature
- Intracranial Hemorrhages
- Hemorrhage
- Premature Birth
- Birth Weight
- Cerebral Hemorrhage
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Reproductive Control Agents
- Gout Suppressants
- Tocolytic Agents
- Indomethacin
Other Study ID Numbers
- R01NS027116 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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