IVHT4: Thyroxine Treatment in Premature Infants With Intraventricular Hemorrhage
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Thyroxine treatment Intravenous thyroxine in a dose of 8 µg/kg/day divided into two doses (every 12 hours) |
Drug: Thyroxine
8 µg/kg/day divided into two doses intravenous every 12 hours
Other Names:
|
| Placebo Comparator: Placebo treatment Intravenous placebo treatment every 12 hours. |
Drug: Placebo
Placebo
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Death or disability [22-26 months of age]
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.
Secondary Outcome Measures
- BSID-IV Motor subscale [22-26 months of age]
Bayley Scales of Infant and Toddler Development (BSID) IV score.
- BSID-IV Cognitive subscale [22-26 months of age]
Bayley Scales of Infant and Toddler Development (BSID) IV score.
- BSID-IV Language subscale [22-26 months of age]
Bayley Scales of Infant and Toddler Development (BSID) IV score.
- Binary composite outcome of death or moderate/severe NDI [22-26 months of age]
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)
- Cerebral palsy incidence and severity [22-26 months of age]
We will perform neurological examination as in PENUT study and GMFCS scoring to determine cerebral palsy incidence and severity
Other Outcome Measures
- MRI studies: dMRI measures (fractional anisotropy; radial, axial and mean diffusivity) in the corpus callosum and corticospinal tract [44+/-1 weeks of postmenstrual age]
dMRI analyses
- MRI studies: myelinated and unmyelinated WM brain volume [44+/-1 weeks of postmenstrual age]
After visual quality control, initial total brain segmentation for tissue types will be done using T2 weighted images with MANTIS, an in-house method of automated Morphologically Adaptive Neonatal Tissue Segmentation (Alexander, et al. 2017)
- MRI studies: Kidokoro WM and global scores [44+/-1 weeks of postmenstrual age]
Kidokoro WM and global scores as in Kidokoro et al ( Am J Neuroradiol 34, 2208-2214:2013)
Eligibility Criteria
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
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Parental consent
Exclusion criteria:
-
Major malformations, including surgical, cardiac, cerebral, chromosomal, or genetic syndromes, identifiable at or before birth;
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Congenital bacterial infection proven by culture at birth or viral syndrome known prior to delivery (e.g. chicken pox, rubella, etc.)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Praveen Ballabh | Bronx | New York | United States | 10461 |
Sponsors and Collaborators
- Albert Einstein College of Medicine
- Westchester Medical Center
- Morgan Stanley Children's Hospital
- University of Pittsburgh
- Children's Minnesota Hospital
- University of Minnesota
- St. Louis University
- Arkansas Children's Hospital Research Institute
- Brigham and Women's Hospital
- University of North Carolina, Chapel Hill
- Wake Forest University Health Sciences
Investigators
- Principal Investigator: PRAVEEN BALLABH, MD, Albert Einstein College of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017-8707