A Randomized Comparative Study Between Liquid (Tirosint®-SOL) and Tablet Formulations of Levothyroxine in Neonates and Infants With Congenital Hypothyroidism
Overview
- Phase
- Phase 4
- Intervention
- Tirosint®-SOL
- Conditions
- Congenital Hypothyroidism
- Sponsor
- IBSA Institut Biochimique SA
- Enrollment
- 34
- Locations
- 10
- Primary Endpoint
- LT4 dose required to maintain TSH in target range (unit: mcg/kg/day)
- Status
- Terminated
- Last Updated
- 6 months ago
Overview
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.
Investigators
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;
Arms & Interventions
Treatment
Tirosint®-SOL (levothyroxine sodium) oral solution (IBSA Pharma Inc.) at the following strengths: 13, 25, 37.5, 44, 50, 62.5, 75, 88, 100 mcg.
Intervention: Tirosint®-SOL
Control
Crushed levothyroxine sodium tablets
Intervention: Levothyroxine Sodium
Outcomes
Primary Outcomes
LT4 dose required to maintain TSH in target range (unit: mcg/kg/day)
Time Frame: Up to 22 months based on age group
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.
Secondary Outcomes
- Growth pattern for length of body(Up to 22 months based on age group)
- Frequency of dose adjustments(Up to 22 months based on age group)
- Number of events of FT4 values below the middle of the laboratory normal range(Up to 22 months based on age group)
- Hormonal profile for FT4(Up to 22 months based on age group)
- Hormonal profile for TSH(Up to 22 months based on age group)
- Parent/caregiver reports of satisfaction and ease of administration(Up to 22 months based on age group)
- Number of events of TSH values above 4.5 mU/L(Up to 22 months based on age group)
- Subject acceptance of the treatment (CareCAT)(Up to 22 months based on age group)
- Signs and symptoms of hypothyroidism(Up to 22 months based on age group)
- Growth pattern for body weight(Up to 22 months based on age group)
- Growth pattern for head circumference(Up to 22 months based on age group)
- Signs and symptoms of hyperthyroidism(Up to 22 months based on age group)