Trial Outcomes & Findings for Indomethacin Germinal Matrix Hemorrhage/Intraventricular Hemorrhage (GMH/IVH) Prevention Trial (NCT NCT00033917)

Results Overview

Cranial ultrasounds were performed daily for the first 5 postnatal days; the main outcome measure was intraaventricular hemorrhage (IVH) at 5 days of age

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

630 participants

Primary outcome timeframe

at 5 days

Results posted on

2013-03-28

Participant Flow

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).

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.

Participant milestones

Participant milestones
Measure	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).	IVH Negative Placebo These subjects also had no evidence for IVH at 6 - 12 hours. They were randomized to an equal volume of placebo.
Overall Study STARTED	209	222
Overall Study COMPLETED	209	222
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Indomethacin n=209 Participants subjects randomized to early low dose indomethacin	Placebo n=222 Participants Group randomized to an equal volume of placebo	Total n=431 Participants Total of all reporting groups
Age Continuous	7.8 hours STANDARD_DEVIATION 2.3 • n=5 Participants	7.9 hours STANDARD_DEVIATION 2.4 • n=7 Participants	7.8 hours STANDARD_DEVIATION 2.3 • n=5 Participants
Sex: Female, Male Female	93 Participants n=5 Participants	103 Participants n=7 Participants	196 Participants n=5 Participants
Sex: Female, Male Male	116 Participants n=5 Participants	119 Participants n=7 Participants	235 Participants n=5 Participants
Region of Enrollment United States	209 participants n=5 Participants	222 participants n=7 Participants	431 participants n=5 Participants

PRIMARY outcome

Timeframe: at 5 days

Population: All subjects had negative cranial ultrasounds with no evidence for IVH at 6 - 12 postnatal hours

Cranial ultrasounds were performed daily for the first 5 postnatal days; the main outcome measure was intraaventricular hemorrhage (IVH) at 5 days of age

Outcome measures

Outcome measures
Measure	Indomethacin n=209 Participants subjects randomized to early low dose indomethacin	Placebo n=222 Participants Group randomized to an equal volume of placebo	Placebo - no IVH Randomized to placebo - no IVH	Placebo - IVH Randomized to placebo; had IVH
IVH at 5 Postnatal Days	25 IVH	40 IVH	—	—

SECONDARY outcome

Timeframe: at 8 years

Population: Three hundred twenty eight subjects were available at age 8 years. They were tested with the PPVT.

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.

Outcome measures

Outcome measures
Measure	Indomethacin n=145 Participants subjects randomized to early low dose indomethacin	Placebo n=20 Participants Group randomized to an equal volume of placebo	Placebo - no IVH n=135 Participants Randomized to placebo - no IVH	Placebo - IVH n=28 Participants Randomized to placebo; had IVH
Language Outcome	12 participants with PPVT score < 70	5 participants with PPVT score < 70	24 participants with PPVT score < 70	7 participants with PPVT score < 70

Adverse Events

IVH Negative Indomethacin

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

IVH Negative Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	IVH Negative Indomethacin n=209 participants at risk；n=208 participants at risk 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).	IVH Negative Placebo n=222 participants at risk These subjects also had no evidence for IVH at 6 - 12 hours. They were randomized to an equal volume of placebo.
Gastrointestinal disorders necrotizing enterocolitis	0.96% 2/209 • Number of events 2 • First 5 postnatal days	0.00% 0/222 • First 5 postnatal days
Renal and urinary disorders decreased urine output	9.1% 19/209 • Number of events 19 • First 5 postnatal days	4.5% 10/222 • Number of events 10 • First 5 postnatal days
Renal and urinary disorders creatinine > 1.8 mg/dL	2.4% 5/209 • Number of events 5 • First 5 postnatal days	2.3% 5/222 • Number of events 5 • First 5 postnatal days
Blood and lymphatic system disorders excessive bleeding	4.3% 9/209 • Number of events 9 • First 5 postnatal days	4.5% 10/222 • Number of events 10 • First 5 postnatal days
Blood and lymphatic system disorders platelets < 50,000	0.96% 2/209 • Number of events 2 • First 5 postnatal days	1.8% 4/222 • Number of events 4 • First 5 postnatal days
Nervous system disorders ischemic changes by ECHO	2.9% 6/209 • Number of events 6 • First 5 postnatal days	5.4% 12/222 • Number of events 12 • First 5 postnatal days

Additional Information

Dr. Laura Ment

Yale University School of Medicine

Phone: 203-785-5708

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place