Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)

Congenital Hypothyroidism Clinical Trial

Official title:

A Randomized Comparative Study Between Liquid (Tirosint®-SOL) and Tablet Formulations of Levothyroxine in Neonates and Infants With Congenital Hypothyroidism

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05228184
• Other study ID #: 20US-T414
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: January 21, 2022
• Est. completion date: April 30, 2025

Study information

• Verified date: April 2024
• Source: IBSA Institut Biochimique SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 126
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 9 Months

Eligibility

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.

Related Conditions & MeSH terms

• Congenital Hypothyroidism
• Hypothyroidism

Intervention

Drug:
• Tirosint®-SOL
Dosage will be according to the USPI and Standard of Care.
• Levothyroxine Sodium
Tablets will be crushed and dissolved in solution. Dosage will be according to the USPI and Standard of Care.

Locations

Country	Name	City	State
United States	Children's Hospital of Atlanta	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cook Children's Health Care Systems	Fort Worth	Texas
United States	Children's Mercy Hospital and Clinics	Kansas City	Missouri
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	CHOC Children's Hospital	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
IBSA Institut Biochimique SA	Cromsource

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to normalize TSH in neonates	Time to normalize TSH into reference range (unit: days)	Up to 28 days
Other	Time to normalize FT4 in neonates	Time to normalize FT4 into the upper half of the laboratory normal FT4 range (unit: days)	Up to 28 days
Primary	LT4 dose required to maintain TSH in target range (unit: mcg/kg/day)	The LT4 dose is calculated based on the daily LT4 dose (mcg) used in the time period preceding the visit (or the average daily dose on a weekly basis if more than one strength is used over the course of the week) and the body weight (kg) measured during the visit.	Up to 22 months based on age group
Secondary	Hormonal profile for TSH	TSH (unit mU/L)	Up to 22 months based on age group
Secondary	Hormonal profile for FT4	FT4 (unit ng/dL)	Up to 22 months based on age group
Secondary	Frequency of dose adjustments	Percent number of subjects (%) who need a dose adjustment in the long-term follow up phase	Up to 22 months based on age group
Secondary	Number of events of TSH values above 4.5 mU/L	TSH value above 4.5 mU/L	Up to 22 months based on age group
Secondary	Number of events of FT4 values below the middle of the laboratory normal range	FT4 value below the middle of the laboratory normal range	Up to 22 months based on age group
Secondary	Growth pattern for length of body	Subject growth measurements in Length (cm) of body	Up to 22 months based on age group
Secondary	Growth pattern for body weight	Subject growth measurements in Body weight (kg)	Up to 22 months based on age group
Secondary	Growth pattern for head circumference	Subject growth measurements in Head circumference (cm)	Up to 22 months based on age group
Secondary	Parent/caregiver reports of satisfaction and ease of administration	Parents Satisfaction Questionnaire is a study-specific tool measuring coping and mental well-being and satisfaction; Score: 1-Strongly disagree, 2-Disagree, 3-Neutral, 4-Agree, 5-Strongly agree.	Up to 22 months based on age group
Secondary	Subject acceptance of the treatment (CareCAT)	Caregiver Administered Children's Acceptance Tool (CareCAT) is a 5-point nominal scale used to assess the acceptance of oral medicines in infants and toddlers who are unable to verbally give their opinion about a medicine	Up to 22 months based on age group
Secondary	Signs and symptoms of hypothyroidism	Total number of subjects experiencing hypothyroidism's signs and symptoms	Up to 22 months based on age group
Secondary	Signs and symptoms of hyperthyroidism	Total number of subjects experiencing hyperthyroidism's signs and symptoms	Up to 22 months based on age group