Congenital Hypothyroidism
Conditions
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.
Interventions
Tablets will be crushed and dissolved in solution. Dosage will be according to the USPI and Standard of Care.
DRUGTirosint®-SOL
Dosage will be according to the USPI and Standard of Care.
Sponsors
IBSA Institut Biochimique SA
Cromsource
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 9 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LT4 Dose Required to Maintain TSH in Target Range (Unit: mcg/kg/Day) | 1 year of age | 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
| Measure | Time frame | Description |
|---|---|---|
| Hormonal Profile for TSH | 1 year of age | TSH (unit mIU/L) |
| Hormonal Profile for FT4 | 1 year of age | FT4 (unit pmol/L) |
| Frequency of Dose Adjustments | Up to 22 months based on age group | Percent number of subjects (%) who need a dose adjustment in the long-term follow up phase |
| Number of Events of TSH Values Above 4.5 mU/L | Up to 22 months based on age group | TSH values above 4.5 mU/L |
| Number of Events of FT4 Values Below the Middle of the Laboratory Normal Range | Up to 22 months based on age group | FT4 values below the middle of the laboratory normal range |
| Growth Pattern for Length of Body | 1 year of age | Subject growth measurements in Length (cm) of body |
| Growth Pattern for Body Weight | 1 year of age | Subject growth measurements in Body weight (kg) |
| Growth Pattern for Head Circumference | 1 year of age | Subject growth measurements in Head circumference (cm) |
| Parent/Caregiver Reports of Satisfaction and Ease of Administration | 3 weeks after treatment start | Parents Satisfaction Questionnaire is a study-specific tool measuring coping and mental well-being and satisfaction in 20 questions. 12 of these questions were scored from 1 to 5, with higher score meaning better outcome. Subject scores were calculated for each subject by visit as mean of the LN(single question score) \[min=0; max=1.61\]. |
| Subject Acceptance of the Treatment (CareCAT) | first treatment week | 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 |
| Signs and Symptoms of Hypothyroidism | Up to 22 months based on age group | Total number of subjects experiencing hypothyroidism's signs and symptoms |
| Signs and Symptoms of Hyperthyroidism | Up to 22 months based on age group | Total number of subjects experiencing hyperthyroidism's signs and symptoms |
Countries
United States
Contacts
STUDY_DIRECTORGiuseppe Mautone
IBSA Head of R&D Scientific Affairs
Participant flow
Pre-assignment details
34 subjects were screened in the study, 31 were randomized. Three subjects were excluded before randomization because of temporary pause of randomization for logistical reasons (2) or for withdrawal by parent/guardian (1)
Baseline characteristics
| Characteristic | — |
|---|---|
| age at randomization | 112.75 days STANDARD_DEVIATION 94.624 |
| Age, Customized infants (age 29 - 277 days of age) | 27 Participants |
| Age, Customized neonates (<28 days of age) | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| free T4 at congenital hypothyroidism diagnosis | 12.30 pmol/L STANDARD_DEVIATION 7.074 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 7 Participants |
| TSH at congenital hypothyroidism diagnosis | 260.17 mIU/L STANDARD_DEVIATION 196.254 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 11 |
| other Total, other adverse events | 15 / 20 | 8 / 11 |
| serious Total, serious adverse events | 2 / 20 | 1 / 11 |
Outcome results
None listed