Thyroxine Treatment in Premature Infants With Intraventricular Hemorrhage

NCT ID: NCT03390530

Last Updated: 2022-07-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-18
• Study Completion Date: 2027-01-18

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.

Conditions

Intraventricular Hemorrhage of Prematurity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Thyroxine treatment

Intravenous thyroxine in a dose of 8 µg/kg/day divided into two doses (every 12 hours)

Group Type: ACTIVE_COMPARATOR

Thyroxine

Intervention Type: DRUG

8 µg/kg/day divided into two doses intravenous every 12 hours

Placebo treatment

Intravenous placebo treatment every 12 hours.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Thyroxine

8 µg/kg/day divided into two doses intravenous every 12 hours

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Levothyroxine; Inactive substance in a similarly looking solution

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.)

• Minimum Eligible Age: 3 Days
• Maximum Eligible Age: 6 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Westchester Medical Center

OTHER

Sponsor Role: collaborator

Morgan Stanley Children's Hospital

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Children's Minnesota Hospital

UNKNOWN

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

St. Louis University

OTHER

Sponsor Role: collaborator

Arkansas Children's Hospital Research Institute

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: collaborator

Albert Einstein College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Praveen Ballabh

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

PRAVEEN BALLABH, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein College of Medicine

Locations

Praveen Ballabh

The Bronx, New York, United States

Countries

United States

Other Identifiers

2017-8707

Identifier Type: -

Identifier Source: org_study_id