1.Problem definition/rationale: Hypothyroidism is among the most common diseases in the general population, for which levothyroxine (LT4) is the standard treatment. A substantial group of patients (~10%) do not feel well on LT4 monotherapy and have persisting debilitating complaints, leading to a poor quality of life. These patients could benefit from the addition of LT3, but results have been contradictory, largely due to a wrong study design.
2.Objectives: To investigate the efficacy of LT4/LT3 combination therapy in hypothyroidism, and what factors (genetic, biochemical, or metabolic profiles) predict its efficacy.
3.Study design: Multicenter double-blind randomized placebo-controlled trial.
4.Patient population: Patients with autoimmune hypothyroidism on LT4 monotherapy with persisting complaints.
5.Investigational product & comparator: LT4/LT3 vs LT4/placebo. Treatment duration: 52 weeks.
6.Outcome variables & assessment: The primary study endpoints are the Hypothyroid Symptoms and the Tiredness scores of the thyroid-specific ThyPRO questionnaire.
7.Analysis: Primary analyses include the mean change from baseline to 52 weeks in the ThyPRO scores.
8.Sample size calculation: With 600 patients we will have 80% power to detect changes of 3.7 and 5.0 points on the Hypothyroid Symptoms and on the Tiredness scales, respectively.
9.Economic evaluation: Cost-utility analysis from a societal perspective.