Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this multicenter trial is to determine if indomethacin prevents bleeding in the brain of very low birth weight preterm infants.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | indomethacin |
|
| 2 | Placebo Comparator | placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| indomethacin | Drug | an anti-inflammatory drug |
| |
| placebo |
| 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 |
| 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 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Laura R. Ment, M.D. | Department of Pediatrics, Yale University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine | New Haven | Connecticut | United States | |||
| Maine Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8134206 | Background | 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. | |
| 8201485 | Background | 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. |
Not provided
Not provided
Cranial ultrasounds were performed on all study participants between 6 - 12 hours of age for group assignment. Subjects with major congenital cerebral malformations were excluded.
Preterm neonates of 600 - 1250 g birth weight were enrolled between 6 and 12 postnatal hours at Yale New Haven Hospital (New Haven, CT), Maine Medical Center (Portland, ME) and Women and Infants' Hospital (Providence, RI).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | IVH Negative Indomethacin | Those subjects with no evidence for intraventricular hemorrhage (IVH) at 6 - 12 postnatal hours. These subjects were randomized to early low-dose indomethacin (0.1 mg/kg/d for 3 doses). |
| FG001 | IVH Negative Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
saline |
|
| Portland |
| Maine |
| United States |
| Brown University School of Medicine | Providence | Rhode Island | United States |
| 8885951 | Background | 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. |
| 9714645 | Background | 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. |
| 10699097 | Background | 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. |
| 11035890 | Background | 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. |
| 12585948 | Background | 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. |
| 16950986 | Background | 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. |
| 19171615 | Background | 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. |
| 19560547 | Background | 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. |
| 19564317 | Background | 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. |
| 20347043 | Background | 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. |
| 21073965 | Background | 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. |
| 21768322 | Background | 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. |
| 22982585 | Background | 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. |
| 15289777 | Background | 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. |
These subjects also had no evidence for IVH at 6 - 12 hours. They were randomized to an equal volume of placebo. |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Indomethacin | subjects randomized to early low dose indomethacin |
| BG001 | Placebo | Group randomized to an equal volume of placebo |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Age is expressed in postnatal hours | Mean | Standard Deviation | hours |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | All subjects had negative cranial ultrasounds with no evidence for IVH at 6 - 12 postnatal hours | Posted | Number | IVH | at 5 days |
|
|
| |||||||||||||||||||||||||||||
| Secondary | 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. | Three hundred twenty eight subjects were available at age 8 years. They were tested with the PPVT. | Posted | Number | participants with PPVT score < 70 | at 8 years |
|
First 5 postnatal days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IVH Negative Indomethacin | Those subjects with no evidence for intraventricular hemorrhage (IVH) at 6 - 12 postnatal hours. These subjects were randomized to early low-dose indomethacin (0.1 mg/kg/d for 3 doses). | 0 | 208 | 19 | 209 | ||
| EG001 | IVH Negative Placebo | These subjects also had no evidence for IVH at 6 - 12 hours. They were randomized to an equal volume of placebo. | 0 | 222 | 12 | 222 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| necrotizing enterocolitis | Gastrointestinal disorders | Non-systematic Assessment | x-ray diagnosis |
| |
| decreased urine output | Renal and urinary disorders | Non-systematic Assessment |
| ||
| creatinine > 1.8 mg/dL | Renal and urinary disorders | Non-systematic Assessment |
| ||
| excessive bleeding | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| platelets < 50,000 | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| ischemic changes by ECHO | Nervous system disorders | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Laura Ment | Yale University School of Medicine | 203-785-5708 | laura.ment@yale.edu |
| ID | Term |
|---|---|
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D007213 | Indomethacin |
| ID | Term |
|---|---|
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| Units | Counts |
|---|---|
| Participants |
|
|