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Study of Thyroid Hormones in Prematures (THOP2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02103998
Recruitment Status : Withdrawn (not funded by NIH)
First Posted : April 4, 2014
Last Update Posted : April 24, 2019
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Edmund F LaGamma, MD, New York Medical College

Brief Summary:
The investigators hypothesize that continuous infusion of 4 µg/Kg/day T4 with 30 µg/Kg/day oral potassium iodide (KI) for 42 days from birth will reduce by 30% or more (from an estimated 30% to 21%) the proportion of extremely low gestational age subjects with a composite endpoint of "cerebral palsy (CP) or a Bayley III Composite Cognitive Score < 85" at 36 months corrected postnatal age (CA).

Condition or disease Intervention/treatment Phase
Transient Hypothyroxinemia of Prematurity (THOP) Drug: thryoid hormone T4 + oral potassium iodide (KI) for 42 days Drug: D5W - 5% dextrose water Phase 3

Detailed Description:
This study is a Phase III multicenter, masked, placebo controlled randomized clinical trial (RCT) of thyroid hormone supplementation in premature infants. Survival for extremely low gestational age neonates (ELGAN; 24 - 28 weeks) has risen to >80% over the past 40 years yet cognitive delays or cerebral palsy (CP) still affect 30% of survivors. Since more than 25,000 ELGANs are born each year in the United States, a major priority in newborn medicine must be to translate the gains in survival into gains in healthy survival without the current high frequency of impairments. Transient hypothyroxinemia of prematurity (THOP) occurs in 50% of ELGANs and is strongly associated as an independent risk factor with lower IQ scores, behavioral abnormalities and CP in ELGANs. Prior evidence suggested a benefit from replacement therapy but studies were underpowered to prove this. The current project extends the findings of our Phase 1 trial (THOP1; R01-NS45109) where four thyroid hormone regimens were tested. We showed that continuous infusion of 4 µg/Kg/day thyroxine x 42d could safely correct transient hypothyroxinemia without markedly lowering TSH - creating a "biochemical euthyroid" state. THOP2 is designed to test the primary hypothesis that compared to placebo, thyroid hormone supplementation from birth will reduce from 30% to 21% the proportion of subjects with a composite endpoint of "CP or a Bayley III Cognitive Score < 85." A Secondary hypothesis is that hormone treatment will improve other measures of cognitive and executive function or attention as assessed by: i) Bayley III Parent Interview for Adaptive Behavior and the BRIEF-P (Behavioral Rating Inventory of Executive Function-Preschool Version) and ii) the frequency of screening positive on the Modified Checklist for Autism in Toddlers (M-CHAT). We plan to enroll 1,224 subjects over a 19.8 month period at 14 centers to obtain 388 surviving toddlers at 36 months corrected age in each of two arms. The current application describes the scientific basis of the proposed overall clinical trial; it is linked to a cluster application creating a Data Monitoring and Analysis Coordinating Center (DCC) at Michigan State University (MSU). The additional societal cost from CP in an affected person's lifetime is estimated at $1 million; the costs of mental retardation are even higher. If this trial shows that an inexpensive intervention can reduce the risks of CP and mental retardation by 30% in ELGANs, we estimate the overall savings from preventing more than 2,000 such cases (9% of 25,000) at about $2 billion per year.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase III Study of Thyroid Hormones in Prematures
Estimated Study Start Date : July 1, 2020
Estimated Primary Completion Date : May 2025
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones Potassium

Arm Intervention/treatment
Experimental: T4 + KI
Continuous infusion of 4 µg/Kg/day T4 with 30 µg/Kg/day oral potassium iodide (KI) for 42 days
Drug: thryoid hormone T4 + oral potassium iodide (KI) for 42 days
Continuous infusion of 4 µg/Kg/day T4 with 30 µg/Kg/day oral potassium iodide (KI) for 42 days
Other Names:
  • levothyroxin
  • postassium iodide

Placebo Comparator: D5W - 5% dextrose water
Receive the same volume as study drug but as D5W placebo
Drug: D5W - 5% dextrose water
Equivalent volume of infusion as study drug
Other Name: Standard hospital pharmacy solution




Primary Outcome Measures :
  1. Compare incidence of a COMPOSITE endpoint of "cerebral palsy (CP) or a Bayley III Composite Cognitive Score < 85" at 36 months corrected postnatal age (CA). [ Time Frame: 36 months ]
    Bayley III Cognitive Score and a standardize ELGAN-type neurological exam (Kuban) plus a Palisano assessment of function


Secondary Outcome Measures :
  1. Compare measures of cognitive and executive function and attention. [ Time Frame: 36 months corrected age ]

    As assessed by the following tests:

    1. The mean scores of the Bayley III Parent Interview for Adaptive Behavior and the BRIEF-P (Behavioral Rating Inventory of Executive Function-Preschool Version).
    2. The frequency of screening positive on the Modified Checklist for Autism in Toddlers (M-CHAT).



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Ages Eligible for Study:   up to 24 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Neonates 24 0/7 to 27 6/7 weeks gestational age
  2. inborn or transferred; < 24 hours old

Exclusion Criteria:

  1. Maternal or congenital thyroid disease or
  2. Maternal substance abuse by history at the time of birth (heroin or cocaine)
  3. Major congenital or surgical malformations of neonate
  4. Known chromosomal anomalies detected by antepartum testing or direct physical examination
  5. Absence of parental consent or treating physician assent
  6. A concurrent clinical trial with another randomized drug
  7. Death expected < 48h vi) Another concern by the treating physician that either mandates or prohibits study treatment such as known adverse drug interaction
  8. mother < 18 years old at delivery

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02103998


Locations
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United States, New York
Maria Fareri Childrens Hospital
Valhalla, New York, United States, 10595
Sponsors and Collaborators
New York Medical College
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Edmund F La Gamma, MD New York Medical College
Publications of Results:
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Responsible Party: Edmund F LaGamma, MD, Professor of Pediatrics, New York Medical College
ClinicalTrials.gov Identifier: NCT02103998    
Other Study ID Numbers: THOP2 - NYMC - CCC
First Posted: April 4, 2014    Key Record Dates
Last Update Posted: April 24, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Edmund F LaGamma, MD, New York Medical College:
extremely low gestational age neonate
hypothyroxinemia of prematurity
brain development
cerebral palsy
cognitive dealy
Additional relevant MeSH terms:
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Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Iodine
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Infective Agents, Local
Anti-Infective Agents
Trace Elements
Micronutrients
Nutrients
Growth Substances