Thyroxine Treatment in Premature Infants With Intraventricular Hemorrhage

Brief Summary
Brain bleed in premature infants damages the brain and survivors suffer from cerebral palsy (weakness in the extremities), cognitive deficits, and neurobehavioral disorders. In this clinical trial, investigators will test whether thyroxine (hormone from thyroid gland) treatment in premature infants with moderate-to-large brain bleeds show recovery in the brain structure on MRI evaluation at the time of discharge (44+/-1 weeks) and neurodevelopmental improvement at 2 years of age.
Brief Title
Thyroxine Treatment in Premature Infants With Intraventricular Hemorrhage
Detailed Description
Intraventricular hemorrhage (IVH) remains a major complication of prematurely born infants. Survivors of IVH suffer from cerebral palsy, cognitive deficits and neurobehavioral disorders. In the proposed study We hypothesize that T4 treatment in preterm (230/7-276/7 weeks) infants with grade II-IV IVH will: a) improve MRI biomarkers, including total myelinated white matter volume, Kidokoro scoring, functional connectivity between motor brain regions, and fractional anisotropy in the corpus callosum of preterm infants with grade II-IV IVH at 36 weeks postmenstrual age, and b) better composite outcome of disability and death. The composite outcome will be derived by integrating scores for Bayley Scales of Infant and Toddler Development (BSID-IV) Motor subscale at 22-26 months in survivors and BSID IV value of 46 assigned to deceased infants. To test these hypotheses, we will perform a randomized double-blinded placebo-controlled trial to determine the effect of T4 treatment on preterm infants with grade II-IV IVH. Ten participating neonatal intensive care units will enroll 346 premature infants (230/7-276/7 weeks gestational age. 173 in each arm) with unilateral or bilateral grade II-IV IVH over a period of 3 years. The treatment will consist of T4 administration (8 µg/kg/day divided into two doses) up to 34 weeks of postmenstrual age, which will be initiated at 2-5 days of postnatal age in all cases. The infants will undergo MRI with DTI at 36 weeks and neurobehavioral evaluation at 22-26 months of corrected age. We have assumed a 7.5 point mean difference (SD=15) in BSID-IV motor subscale between T4 and placebo groups, an overall mortality rate of 25%, and 5% reduction in mortality for each SD change in outcome. Based on these, we expect an increase in the induced composite outcome by ≥5.6 points in T4 treated group compared to placebo controls. The study will conclusively determine whether the proposed clinical trial of T4 treatment enhances motor outcome and diminishes composite endpoint of death or disability in preterm infants with grade II-IV IVH.
Completion Date
Completion Date Type
Estimated
Conditions
Intraventricular Hemorrhage of Prematurity
Eligibility Criteria
Inclusion Criteria

* NICU inpatients born between 23-0/7 and 27-6/7 weeks of gestation
* Postnatal age 3-6days (≥3 d ≤ 6 d)
* Unilateral or bilateral Grade 3 or 4 IVH
* Parental consent

Exclusion criteria:

* Major malformations, including surgical, cardiac, cerebral, chromosomal, or genetic syndromes, identifiable at or before birth;
* Congenital bacterial infection proven by culture at birth or viral syndrome known prior to delivery (e.g. chicken pox, rubella, etc.)
Inclusion Criteria
Inclusion Criteria

* NICU inpatients born between 23-0/7 and 27-6/7 weeks of gestation
* Postnatal age 3-6days (≥3 d ≤ 6 d)
* Unilateral or bilateral Grade 3 or 4 IVH
* Parental consent

Gender
All
Gender Based
false
Keywords
Thyroxine
Intraventricular hemorrhage
MRI with DTI,
Neurodevelopmental outcome
Healthy Volunteers
No
Last Update Submit Date
Maximum Age
6 Days
Minimum Age
3 Days
NCT Id
NCT03390530
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2017-8707
Overall Status
Withdrawn
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Thyroxine Treatment in Premature Infants With Intraventricular Hemorrhage: Phase III Clinical Trial
Primary Outcomes
Outcome Description
The primary outcome will be a quantitative composite outcome using the BSID-IV Motor score measured at 22-26 months among survivors while incorporating death using a floor value of 46.
Outcome Measure
Death or disability
Outcome Time Frame
22-26 months of age
Secondary Outcomes
Outcome Description
Bayley Scales of Infant and Toddler Development (BSID) IV score.
Outcome Time Frame
22-26 months of age
Outcome Measure
BSID-IV Motor subscale
Outcome Description
Bayley Scales of Infant and Toddler Development (BSID) IV score.
Outcome Time Frame
22-26 months of age
Outcome Measure
BSID-IV Cognitive subscale
Outcome Description
Bayley Scales of Infant and Toddler Development (BSID) IV score.
Outcome Time Frame
22-26 months of age
Outcome Measure
BSID-IV Language subscale
Outcome Description
NDI will be defined as the presence of any of the following: BSID-IV Cognitive \< 85, BSID-IV Motor \<85, GMFCS ≥ 2 (NICHD, Neonatal Res. Network 2018)
Outcome Time Frame
22-26 months of age
Outcome Measure
Binary composite outcome of death or moderate/severe NDI
Outcome Description
We will perform neurological examination as in PENUT study and GMFCS scoring to determine cerebral palsy incidence and severity
Outcome Time Frame
22-26 months of age
Outcome Measure
Cerebral palsy incidence and severity
Start Date
Start Date Type
Estimated
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
0
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Praveen Ballabh
Investigator Email
praveen.ballabh@einsteinmed.org
Investigator Phone