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