Intraventricular Hemorrhage (IVH)Phase 3NCT00033917
Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial
A Phase 3 study testing indomethacin in people with Intraventricular Hemorrhage (IVH) and Bleeding in the Brain, run by Yale University at 3 sites in United States.
Trial summary
The purpose of this multicenter trial is to determine if indomethacin prevents bleeding in the brain of very low birth weight preterm infants. Read more about this study
- Who is it for?
- Ages Up to 6 hoursHealthy volunteers can take part
- Conditions the study is for
- Intraventricular Hemorrhage (IVH), Bleeding in the Brain, Prematurity
- What is being tested?
- indomethacin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 630 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 1989to Mar 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 hours
- All sexes
- Healthy volunteers accepted
- Child
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Yale University School of Medicine
New Haven, Connecticut
Maine Medical Center
Portland, Maine
Brown University School of Medicine
Providence, Rhode Island
About this study
Official title: Randomized Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial
The purpose of this multicenter trial is to determine if indomethacin prevents bleeding in the brain of very low birth weight preterm infants.
Read the 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.
- Conditions
- Intraventricular Hemorrhage (IVH), Bleeding in the Brain, Prematurity, Very Low Birth Weight Infants
- Being tested
- indomethacin, placebo
- Keywords
- intraventricular hemorrhage (IVH), bleeding in the brain, indomethacin, prematurity, very low birth weight infants
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
indomethacinDrug
an anti-inflammatory drug
placeboDrug
saline
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | indomethacin Receives: Drug: indomethacin |
| 2 | Placebo comparator | placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: at 5 days
Secondary outcomes (1)
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.
Measured: at 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2002 (estimated)
- Study startSep 1989
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Intraventricular Hemorrhage (IVH)Studies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 630 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Laura R. Ment, Yale University
- Investigators
- Laura R. Ment, M.D., Principal investigator, Department of Pediatrics, Yale University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00033917
- Sponsor's protocol ID
- R01NS027116
- Status last verified
- Feb 2013
- First submitted
- 12 Apr 2002
- Last updated
- 28 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 8134206Ment 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.
PubMed 8201485Ment 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.
PubMed 8885951Ment 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.
PubMed 9714645Ment 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.
PubMed 10699097Peterson 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.
PubMed 11035890Ment 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.
PubMed 12585948Ment 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.
PubMed 16950986Ment 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.
PubMed 19171615Gozzo 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.
PubMed 19560547Luu 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.
PubMed 19564317Myers 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.
PubMed 20347043Mullen 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.
PubMed 21073965Luu 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.
PubMed 21768322Constable 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.
PubMed 22982585
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial
- ClinicalTrials.gov ID
- NCT00033917
- Acronym / sponsor ID
- R01NS027116
- Conditions
- Intraventricular Hemorrhage (IVH), Bleeding in the Brain, Prematurity, Very Low Birth Weight Infants
- Keywords
- intraventricular hemorrhage (IVH), bleeding in the brain, indomethacin, prematurity, very low birth weight infants
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 630 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Sep 1989
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 15 Apr 2002 (estimated)
- Results
- Posted 28 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: indomethacinindomethacin |
| 2 | Placebo comparator | Drug: placeboplacebo |
Who may qualify
- Ages
- Up to 6 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| indomethacinan anti-inflammatory drug | Drug | 1 |
| placebosaline | Drug | 2 |
Primary outcome
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
1 secondary outcome
Language Outcome
Time frame: at 8 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8134206Ment 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.
- Background: PubMed 8201485Ment 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.
- Background: PubMed 8885951Ment 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.
- Background: PubMed 9714645Ment 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.
- Background: PubMed 10699097Ment 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.
- Background: PubMed 11035890Peterson 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.
- Background: PubMed 12585948Ment 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.
- Background: PubMed 16950986Ment 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.
- Background: PubMed 19171615Ment 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.
- Background: PubMed 19560547Gozzo 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.
- Background: PubMed 19564317Luu 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.
- Background: PubMed 20347043Myers 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura R. Ment, M.D. principal investigator
Department of Pediatrics, Yale University School of Medicine
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing indomethacin in people with Intraventricular Hemorrhage (IVH) and Bleeding in the Brain, run by Yale University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IVH at 5 Postnatal Days (time frame: at 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00033917, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2013.