Transient Hypothyroxinemia of Prematurity (THOP)Phase 3THOP2NCT02103998
Study of Thyroid Hormones in Prematures
A Phase 3 study testing thryoid hormone T4 + oral potassium iodide (KI) for 42 days and D5W - 5% dextrose water in people with Transient Hypothyroxinemia of Prematurity (THOP), run by New York Medical College at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 hour to 24 hoursHealthy volunteers can take part
- Conditions the study is for
- Transient Hypothyroxinemia of Prematurity (THOP)
- What is being tested?
- thryoid hormone T4 + oral potassium iodide (KI) for 42 days and D5W - 5% dextrose water
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2020to May 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 24 hours
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Neonates 24 0/7 to 27 6/7 weeks gestational age
- inborn or transferred; < 24 hours old
Who cannot join
- Maternal or congenital thyroid disease or
- Maternal substance abuse by history at the time of birth (heroin or cocaine)
- Major congenital or surgical malformations of neonate
- Known chromosomal anomalies detected by antepartum testing or direct physical examination
- Absence of parental consent or treating physician assent
- A concurrent clinical trial with another randomized drug
- Death expected < 48h vi) Another concern by the treating physician that either mandates or prohibits study treatment such as known adverse drug interaction
- mother < 18 years old at delivery
Trial locations and contacts
1 site in 1 country.
United States1 site
Maria Fareri Childrens Hospital
Valhalla, New York, 10595
About this study
Official title: Phase III Study of Thyroid Hormones in Prematures
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).
Read the 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.
- Being tested
- thryoid hormone T4 + oral potassium iodide (KI) for 42 days, D5W - 5% dextrose water
- Keywords
- extremely low gestational age neonate, hypothyroxinemia of prematurity, brain development, cerebral palsy, cognitive dealy
- Medical subject headings
- Cerebral Palsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
thryoid hormone T4 + oral potassium iodide (KI) for 42 daysDrug
Also called levothyroxin, postassium iodide
Continuous infusion of 4 µg/Kg/day T4 with 30 µg/Kg/day oral potassium iodide (KI) for 42 days
D5W - 5% dextrose waterDrug
Also called Standard hospital pharmacy solution
Equivalent volume of infusion as study drug
| Study group | Role | What they receive |
|---|---|---|
| T4 + KI | Experimental | Continuous infusion of 4 µg/Kg/day T4 with 30 µg/Kg/day oral potassium iodide (KI) for 42 days Receives: Drug: thryoid hormone T4 + oral potassium iodide (KI) for 42 days |
| D5W - 5% dextrose water | Placebo comparator | Receive the same volume as study drug but as D5W placebo Receives: Drug: D5W - 5% dextrose water |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Bayley III Cognitive Score and a standardize ELGAN-type neurological exam (Kuban) plus a Palisano assessment of function
Measured: 36 months
Secondary outcomes (1)
Compare measures of cognitive and executive function and attention.
As assessed by the following tests:
- The mean scores of the Bayley III Parent Interview for Adaptive Behavior and the BRIEF-P (Behavioral Rating Inventory of Executive Function-Preschool Version).
- The frequency of screening positive on the Modified Checklist for Autism in Toddlers (M-CHAT).
Measured: 36 months corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2014 (estimated)
- Study start1 Jul 2020 (estimated)
- Primary completionMay 2025 (estimated)
- Study completionMay 2026 (estimated)
Why it stopped: not funded by NIH
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transient Hypothyroxinemia of Prematurity (THOP)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York Medical College
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Edmund F LaGamma, MD, New York Medical College
- Investigators
- Edmund F La Gamma, MD, Principal investigator, New York Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02103998
- Sponsor's protocol ID
- THOP2 - NYMC - CCC
- Acronym
- THOP2
- Status last verified
- Apr 2019
- First submitted
- 2 May 2013
- Last updated
- 24 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
La Gamma EF, van Wassenaer AG, Ares S, Golombek SG, Kok JH, Quero J, Hong T, Rahbar MH, de Escobar GM, Fisher DA, Paneth N. Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks' gestation. Pediatrics. 2009 Aug;124(2):e258-68. doi: 10.1542/peds.2008-2837. Epub 2009 Jul 5.
PubMed 19581264
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Thyroid Hormones in Prematures
- ClinicalTrials.gov ID
- NCT02103998
- Acronym / sponsor ID
- THOP2 / THOP2 - NYMC - CCC
- Keywords
- extremely low gestational age neonate, hypothyroxinemia of prematurity, brain development, cerebral palsy, cognitive dealy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: not funded by NIH
- Enrolment
- 0 participants (actual)
- Lead sponsor
- New York Medical CollegeUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 1 Jul 2020 (estimated)
- Primary completion
- May 2025 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 4 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| T4 + KI | Experimental | Drug: thryoid hormone T4 + oral potassium iodide (KI) for 42 daysContinuous infusion of 4 µg/Kg/day T4 with 30 µg/Kg/day oral potassium iodide (KI) for 42 days |
| D5W - 5% dextrose water | Placebo comparator | Drug: D5W - 5% dextrose waterReceive the same volume as study drug but as D5W placebo |
Who may qualify
- Ages
- 1 hour to 24 hours
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Neonates 24 0/7 to 27 6/7 weeks gestational age
- inborn or transferred; < 24 hours old
Key exclusion criteria (8 listed)
- Maternal or congenital thyroid disease or
- Maternal substance abuse by history at the time of birth (heroin or cocaine)
- Major congenital or surgical malformations of neonate
- Known chromosomal anomalies detected by antepartum testing or direct physical examination
- Absence of parental consent or treating physician assent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| thryoid hormone T4 + oral potassium iodide (KI) for 42 daysAlso: levothyroxin, postassium iodideContinuous infusion of 4 µg/Kg/day T4 with 30 µg/Kg/day oral potassium iodide (KI) for 42 days | Drug | T4 + KI |
| D5W - 5% dextrose waterAlso: Standard hospital pharmacy solutionEquivalent volume of infusion as study drug | Drug | D5W - 5% dextrose water |
Primary outcome
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
1 secondary outcome
Compare measures of cognitive and executive function and attention.
Time frame: 36 months corrected age
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2019.
- Results publication: PubMed 19581264La Gamma EF, van Wassenaer AG, Ares S, Golombek SG, Kok JH, Quero J, Hong T, Rahbar MH, de Escobar GM, Fisher DA, Paneth N. Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks' gestation. Pediatrics. 2009 Aug;124(2):e258-68. doi: 10.1542/peds.2008-2837. Epub 2009 Jul 5.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edmund F La Gamma, MD principal investigator
New York Medical College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing thryoid hormone T4 + oral potassium iodide (KI) for 42 days and D5W - 5% dextrose water in people with Transient Hypothyroxinemia of Prematurity (THOP), run by New York Medical College at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02103998, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2019.