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Antithyroid Drug Treatment of Thyrotoxicosis in Young People

Information source: Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Paediatric Thyrotoxicosis

Intervention: Block and Replace (Procedure); Dose Titration (Procedure); carbimazole (Drug); propylthiouracil (Drug); thyroxine (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Newcastle-upon-Tyne Hospitals NHS Trust

Official(s) and/or principal investigator(s):
Tim Cheetham, Principal Investigator, Affiliation: Newcastle upon Tyne Hospiatls NHS Foundation Trust


The investigators aim to establish whether biochemical control during anti-thyroid drug therapy in young people with thyrotoxicosis varies depending upon whether a 'block and replace' or 'dose titration' regimen is used. The investigators will also assess remission rates and the frequency of side-effects in the two treatment groups.

Clinical Details

Official title: A Randomised Study of Two Anti-thyroid Drug Treatment Regimens in Young People

Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Biochemical control as reflected by the stability of blood thyroid stimulating hormone (TSH) concentrations

Secondary outcome:

Remission rates as defined by patients who are biochemically euthyroid at the end of the 4 year study period.

The frequency of adverse events on the 2 treatment regimens.

Additional measures of biochemical control.

Detailed description: Thyrotoxicosis is an uncommon disorder in childhood and adolescence with a UK incidence around 1 per 100,000 (0-15 years). Most patients with thyrotoxicosis have Graves' disease which develops because of thyrotropin (TSH) receptor stimulation by autoantibodies. Patients with Hashimoto's thyroiditis can also be thyrotoxic in the early phase of the disease and occasionally thyrotoxicosis develops because of activating mutations of the TSH receptor. Many general paediatricians have experience of managing patients with thyrotoxicosis but national guidelines to assist in patient care have not been produced to date. There is no ideal therapy for thyrotoxicosis in children and adolescents. The three

treatment modalities for thyrotoxicosis - anti-thyroid drugs (ATD), surgery and radioiodine

all have significant disadvantages. Particular considerations when managing young people include: 1. Low remission rates following a course of ATD. 2. Concerns about the morbidity associated with thyroidectomy. 3. Inadequate data regarding the long term safety of radioiodine. Children and adolescents presenting with autoimmune thyrotoxicosis in the UK are usually

treated with ATD from diagnosis for 1 - 4 years. Treatment is then stopped and patients who

relapse return to ATD or are offered more definitive treatment with surgery or radioiodine. Life-long thyroid hormone replacement will be required if the thyroid gland is removed by surgery or ablated by radioiodine. Excess thyroid hormone can have a major detrimental impact on cognitive function as well as cardiovascular and skeletal health. The maintenance of a clinically and biochemically euthyroid state is therefore highly desirable. There are two possible approaches when treating patients with ATD.

- 'Block and replace' (combined) therapy - where thyroid hormone production is prevented

by ATD and thyroxine is then added in a replacement dose.

- 'Dose titration' (adaptive) therapy - where the dose of ATD is adjusted so that hormone

production is normalised. Both strategies are used by adult endocrinologists but it is unclear which of these approaches is the most appropriate in the young person. Potential advantages of the 'block and replace' regimen include:

- Improved stability with fewer episodes of hyper or hypothyroidism.

- A reduced number of venepunctures and visits to hospital.

- Improved remission rates following a larger anti-thyroid drug dose.

Potential advantages of the dose titration approach include:

- Fewer side effects with a lower anti-thyroid drug dose

- Improved compliance on one rather than two medications. A meta-analysis conducted

primarily in adult patients concluded that 'dose titration' was the most appropriate way to manage thyrotoxicosis because of fewer ATD-related side-effects although a group of authors subsequently highlighted significant limitations of this study.

This study is a prospective, multi-centre trial which aims to establish which regimen -

block and replace or dose titration - is the most appropriate medical therapy for

thyrotoxicosis during childhood and adolescence.

- Primary completion date changed from January 2019 to November 2014

- Study completion date changed from January 2019 to November 2015


Minimum age: 2 Years. Maximum age: 16 Years. Gender(s): Both.


Inclusion Criteria: 1. All patients with thyrotoxicosis aged between 2 and 16 years at the time of diagnosis. Thyrotoxicosis will be diagnosed by the paediatrician on the basis of the clinical picture and the biochemistry (suppressed TSH with high thyroid hormone levels). 2. Child has consented/assented or consent via parent/guardian has been gained prior to any study specific procedures Exclusion Criteria: 1. Known toxic adenoma / toxic hyperplasia (germline activating TSHR mutation). 2. McCune Albright Syndrome. 3. Previous episodes of Thyrotoxicosis.. 4. Known allergic response to any of the study medication or ingredients as per SmPC. 5. Previous participation in this study.

Locations and Contacts

Royal Aberdeen Children's Hospital, Aberdeen, United Kingdom

Birmingham Children's Hospital, Birmingham, United Kingdom

Addebrookes Hospital, Cambridge, United Kingdom

Wales College of Medicine, Cardiff, United Kingdom

University Hospital, Coventry, United Kingdom

Ninewells Hospital, Dundee, United Kingdom

Royal Hospital for Sick Children, Edinburgh, United Kingdom

Royal Hospital for Sick Children, Glasgow, United Kingdom

Hereford Hospital, Hereford, United Kingdom

Crosshouse Hospital, Kilmarnock, United Kingdom

Alder Hey Children's Hospital, Liverpool, United Kingdom

St Bart's Hospital, London, United Kingdom

St George's Hospital, London, United Kingdom

Royal Manchester Children's Hospital, Manchester, United Kingdom

Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom

Norfolk & Norwich University Hospitals, Norwich, United Kingdom

Oxford Radcliffe Hospitals, Oxford, United Kingdom

Sheffield Children's Hospital, Sheffield, United Kingdom

Additional Information

British Society for Paediatric Endocrinology and Diabetes supports this study

Starting date: July 2004
Last updated: May 7, 2015

Page last updated: August 23, 2015

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