Clinical trial NCT03390530: Thyroxine Treatment in Premature Infants With Intraventricular Hemorrhage
Official title: Thyroxine Treatment in Premature Infants With Intraventricular Hemorrhage: Phase III Clinical Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Intraventricular Hemorrhage of Prematurity
Keywords: Thyroxine
Intraventricular hemorrhage
MRI with DTI,
Neurodevelopmental outcome
Lead sponsor: Albert Einstein College of Medicine
Sponsor class: OTHER
Collaborators: name: Westchester Medical Center
name: Morgan Stanley Children's Hospital
name: University of Pittsburgh
name: Children's Minnesota Hospital
name: University of Minnesota
name: St. Louis University
name: Arkansas Children's Hospital Research Institute
name: Brigham and Women's Hospital
name: University of North Carolina, Chapel Hill
name: Wake Forest University Health Sciences
First posted: 2018-01-04
Enrollment: 0
Sex: ALL
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blinded, placebo-controlled, and randomized controlled trial to compare outcomes between thyroxine and placebo treatment
Primary purpose: TREATMENT

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.

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.

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.)

Primary outcomes:
measure: Death or disability
timeFrame: 22-26 months of age
Secondary outcomes:
measure: BSID-IV Motor subscale
timeFrame: 22-26 months of age
measure: BSID-IV Cognitive subscale
timeFrame: 22-26 months of age
measure: BSID-IV Language subscale
timeFrame: 22-26 months of age
measure: Binary composite outcome of death or moderate/severe NDI
timeFrame: 22-26 months of age
measure: Cerebral palsy incidence and severity
timeFrame: 22-26 months of age
Other outcomes:
measure: MRI studies: dMRI measures (fractional anisotropy; radial, axial and mean diffusivity) in the corpus callosum and corticospinal tract
timeFrame: 44+/-1 weeks of postmenstrual age
measure: MRI studies: myelinated and unmyelinated WM brain volume
timeFrame: 44+/-1 weeks of postmenstrual age
measure: MRI studies: Kidokoro WM and global scores
timeFrame: 44+/-1 weeks of postmenstrual age
Locations:
city: Bronx
country: United States
facility: Praveen Ballabh
state: New York
Study officials:
affiliation: Albert Einstein College of Medicine
name: PRAVEEN BALLABH, MD
role: PRINCIPAL_INVESTIGATOR
References: