Clinical trial NCT05228184: Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)
Official title: A Randomized Comparative Study Between Liquid (Tirosint®-SOL) and Tablet Formulations of Levothyroxine in Neonates and Infants With Congenital Hypothyroidism
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Congenital Hypothyroidism
Lead sponsor: IBSA Institut Biochimique SA
Sponsor class: INDUSTRY
Collaborators: name: Cromsource
First posted: 2022-02-08
Enrollment: 34
Sex: ALL
Minimum age (years): 1
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, prospective, parallel-group, open-label, randomized clinical study in one hundred and twenty-six (126) neonates and infants diagnosed with CH.

Subjects will be randomized in a 2:1 ratio to Treatment (Tirosint®-SOL) or Control (conventional therapy with levothyroxine sodium crushed tablets).

Detailed description: Newly diagnosed neonates will be randomly assigned to start therapy with LT4 at the initial dose recommended by the Standard of Care (SOC). Infants already on LT4 therapy will continue at the same daily dose within the randomly assigned treatment group (dose adjustments are allowed, if needed based on laboratory parameters and clinical response). Once enrolled, subjects will be treated and followed for 12 months (±1.5 months), participating in 7-8 study visits, consisting of 6-7 inclinic and 1-2 (or more if follow-up visits are required) telemedicine (TM) visits. The total number of visits depends on the age at inclusion.

Eligibility criteria: Inclusion Criteria:

* Male and female patient aged 0 to 9 months
* Primary CH diagnosis with elevated TSH and low or normal FT4, requiring treatment with LT4, under either of the following conditions:

  * Neonates newly diagnosed with primary CH and needing to initiate LT4 therapy, or
  * Infants previously diagnosed with primary CH and who are already on LT4 therapy for at least 3 weeks;
* Provide and comply with the informed consent.

Exclusion Criteria:

* Preterm neonates with a gestational age \< 37 weeks;
* Low birth weight (LBW) or very low birth weight (VLBW) neonates (weight \< 2.5 kg) or VLBW infants (weight \< 1.5 kg);
* Neonates in neonatal intensive care units or requiring admission to NICU or neonates/infants hospitalized or requiring hospitalization or in fragile health conditions (e.g. with serious health problems or complications);
* Neonates with CH diagnosis \> 4 weeks after delivery;
* Diagnosis of primary gastrointestinal disease:

  * Gastroesophageal reflux requiring medical therapy (beyond thickening of formula or position);
  * Anatomic defects (e.g. intestinal atresia, malrotation, tracheoesophageal fistula, pyloric stenosis, Hirschsprung's disease, gastroschisis);
  * Dietary allergy (e.g. cow's milk protein allergy);
  * Malabsorption related to cystic fibrosis, celiac disease and others;
  * Necrotizing enterocolitis requiring surgical resection;
* Known or suspected adrenal insufficiency (e.g. congenital adrenal hyperplasia, hypopituitarism);
* Diagnosis of congenital cardiac disease, cardiac insufficiency or risk for cardiac failure;
* Diagnosis of chromosomopathy;
* Diagnosis of central hypothyroidism;
* Hypersensitivity to glycerol;
* Concomitant anticonvulsant medications, liothyronine, combination of LT4 and liothyronine, thyroid extracts and/or chronic or long-term use of systemic glucocorticoids
* History of nonadherence with medication or medical visit schedule; or
* Any condition for which, participation would not be in the best interest of the patient or that could limit protocol specified assessments.

Primary outcomes:
measure: LT4 dose required to maintain TSH in target range (unit: mcg/kg/day)
timeFrame: Up to 22 months based on age group
Secondary outcomes:
measure: Hormonal profile for TSH
timeFrame: Up to 22 months based on age group
measure: Hormonal profile for FT4
timeFrame: Up to 22 months based on age group
measure: Frequency of dose adjustments
timeFrame: Up to 22 months based on age group
measure: Number of events of TSH values above 4.5 mU/L
timeFrame: Up to 22 months based on age group
measure: Number of events of FT4 values below the middle of the laboratory normal range
timeFrame: Up to 22 months based on age group
measure: Growth pattern for length of body
timeFrame: Up to 22 months based on age group
measure: Growth pattern for body weight
timeFrame: Up to 22 months based on age group
measure: Growth pattern for head circumference
timeFrame: Up to 22 months based on age group
measure: Parent/caregiver reports of satisfaction and ease of administration
timeFrame: Up to 22 months based on age group
measure: Subject acceptance of the treatment (CareCAT)
timeFrame: Up to 22 months based on age group
measure: Signs and symptoms of hypothyroidism
timeFrame: Up to 22 months based on age group
measure: Signs and symptoms of hyperthyroidism
timeFrame: Up to 22 months based on age group
Other outcomes:
measure: Time to normalize TSH in neonates
timeFrame: Up to 28 days
measure: Time to normalize FT4 in neonates
timeFrame: Up to 28 days
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Orange
country: United States
facility: CHOC Children's Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Children's Hospital of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinics
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Health Care Systems
state: Texas
Study officials:
affiliation: IBSA Head of R&D Scientific Affairs
name: Giuseppe Mautone
role: STUDY_DIRECTOR
References: