Randomised Trial of Block and Replace versus dose titration antithyroid drug treatment in children and adolescents with thyrotoxicosis.

This dataset contains the study regimens for the randomised controlled trial.

Context

First line treatment of thyrotoxicosis in young people is thionamide antithyroid drug (ATD) in a blocking dose with levothyroxine replacement (block and replace, BR) or in a smaller dose tailored to render the patient euthyroid (dose titration, DT). 

Objective

To determine which regimen provides more stable biochemical control. 

Design and setting

A multi-centre phase III, open-label randomised trial comparing BR with DT in patients aged 2 to 16 years with newly diagnosed thyrotoxicosis at 15 UK centres. Patients were randomised shortly after diagnosis and treated for 3 years. The primary outcome was the percentage of serum thyroid stimulating hormone (TSH) levels in the reference range between 6 months and 3 years.  Secondary outcomes included the proportion of Free thyroxine (FT4) levels in the reference range, adverse event frequency and 4y outcome (remission/relapse).

Results

Eighty-two patients were randomised, with details on clinical course in 81 (62 Female); 40 were allocated to BR (41 DT). Three withdrew with one ineligible. The mean percentage of serum TSH within reference range was 60·2% in BR and 63·8% in DT patients; adjusted difference 4·3%, 95% CI (-7·8 to 16·4);p=0.48. Proportions for FT4 were 79·2% in BR and 85·7% in DT patients; adjusted difference 6·8%, (-0·2 to 15·6);p=0·13.  Three patients developed neutropenia – all on BR. 6 BR and 10 DT patients were in remission at 4y.  

Conclusion

This trial has shown no evidence to suggest that BR improves biochemical stability. DT, recommended by American Thyroid Association guidelines, remains the preferred approach in this age group.