Antithyroid Drug Treatment of Thyrotoxicosis in Young People
NCT ID: NCT01436994
Last Updated: 2016-09-21
Study Results
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Basic Information
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COMPLETED
PHASE3
81 participants
INTERVENTIONAL
2004-07-31
2015-11-30
Brief Summary
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Detailed Description
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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
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Block and Replace
Carbimazole is commenced in a dose of 0.75 mg/kg/day. The intention is to completely prevent endogenous thyroxine production. Thyroxine is then added in a replacement dose as the thyroid hormone levels fall into the lower half of the laboratory normal range. The principal measure of control during the first 6 months will be thyroid hormone levels rather than TSH.
Block and Replace
The primary objective of treatment is to maintain a euthyroid state with TSH and thyroid hormone levels in the local laboratory normal range. Carbimazole is commenced in a dose of 0.75 mg/kg/day (propylthiouracil - for dose see below) with the aim being to completely preventing endogenous thyroxine production. Thyroxine is then added in a low replacement dose as the thyroid hormone levels fall into the lower half of the laboratory normal range. The principle measure of control during the first 6 months will be thyroid hormone levels rather than TSH. Carbimazole is the preferred treatment because of the increased risk of hepatotoxicity with propylthiouracil but patients who are treated with propylthiouracil can also be recruited and randomised. 1mg of carbimazole is approximately equivalent to 10 mg of propylthiouracil.
carbimazole
Carbimazole 5mg and 20 mg tablets Administered as a once or twice daily regimen with total daily dose adjusted according to prevailing biochemistry
propylthiouracil
50 mg tablets administered once daily with the dose adjusted according to the prevailing biochemistry
thyroxine
25mcg, 50mcg and 100mcg tabletes administered once daily with the dose adjusted according to the prevailing biochemistry
Dose Titration
Carbimazole is commenced in a dose of 0.75 mg/kg/day until thyroid hormone levels fall into the local laboratory normal range. The dose is then reduced to 0.25 mg/kg/day with the intention of maintaining the euthyroid state. The principal measure of control during the first 6 months will be thyroid hormone levels rather than TSH.
Carbimazole is the preferred treatment because of the increased risk of hepatotoxicity with propylthiouracil but patients who are treated with propylthiouracil can also be recruited and randomised. 1mg of carbimazole is approximately equivalent to 10 mg of propylthiouracil.
Drug: Carbimazole 5mg and 20 mg tablets. Administered as a once or twice daily regimen with total daily dose adjusted according to prevailing biochemistry Drug: propylthiouracil 50 mg tablets administered once daily with the dose adjusted according to the prevailing biochemistry.
Dose Titration
The primary objective of treatment is to maintain a euthyroid state with TSH and thyroid hormone levels in the local laboratory normal range.
Carbimazole is commenced in a dose of 0.75 mg/kg/day until thyroid hormone levels fall into the local laboratory normal range. The dose is then reduced to 0.25 mg/kg/day with the intention of maintaining a euthyroid state as reflected by a free thyroxine and TSH within the normal range.
Most paediatricians in the UK commence thyrotoxic children on carbimazole rather than propylthiouracil. Carbimazole is the preferred treatment because of the increased risk of hepatotoxicity with propylthiouracil but patients who are treated with propylthiouracil can also be recruited and randomised. The guidelines detailed above can be used in the knowledge that 1mg of carbimazole is approximately equivalent to 10 mg of propylthiouracil.
carbimazole
Carbimazole 5mg and 20 mg tablets Administered as a once or twice daily regimen with total daily dose adjusted according to prevailing biochemistry
propylthiouracil
50 mg tablets administered once daily with the dose adjusted according to the prevailing biochemistry
Interventions
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Block and Replace
The primary objective of treatment is to maintain a euthyroid state with TSH and thyroid hormone levels in the local laboratory normal range. Carbimazole is commenced in a dose of 0.75 mg/kg/day (propylthiouracil - for dose see below) with the aim being to completely preventing endogenous thyroxine production. Thyroxine is then added in a low replacement dose as the thyroid hormone levels fall into the lower half of the laboratory normal range. The principle measure of control during the first 6 months will be thyroid hormone levels rather than TSH. Carbimazole is the preferred treatment because of the increased risk of hepatotoxicity with propylthiouracil but patients who are treated with propylthiouracil can also be recruited and randomised. 1mg of carbimazole is approximately equivalent to 10 mg of propylthiouracil.
Dose Titration
The primary objective of treatment is to maintain a euthyroid state with TSH and thyroid hormone levels in the local laboratory normal range.
Carbimazole is commenced in a dose of 0.75 mg/kg/day until thyroid hormone levels fall into the local laboratory normal range. The dose is then reduced to 0.25 mg/kg/day with the intention of maintaining a euthyroid state as reflected by a free thyroxine and TSH within the normal range.
Most paediatricians in the UK commence thyrotoxic children on carbimazole rather than propylthiouracil. Carbimazole is the preferred treatment because of the increased risk of hepatotoxicity with propylthiouracil but patients who are treated with propylthiouracil can also be recruited and randomised. The guidelines detailed above can be used in the knowledge that 1mg of carbimazole is approximately equivalent to 10 mg of propylthiouracil.
carbimazole
Carbimazole 5mg and 20 mg tablets Administered as a once or twice daily regimen with total daily dose adjusted according to prevailing biochemistry
propylthiouracil
50 mg tablets administered once daily with the dose adjusted according to the prevailing biochemistry
thyroxine
25mcg, 50mcg and 100mcg tabletes administered once daily with the dose adjusted according to the prevailing biochemistry
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Child has consented/assented or consent via parent/guardian has been gained prior to any study specific procedures
Exclusion Criteria
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.
2 Years
16 Years
ALL
No
Sponsors
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Newcastle-upon-Tyne Hospitals NHS Trust
OTHER
Responsible Party
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Tim Cheetham
Dr Tim Cheetham
Principal Investigators
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Tim Cheetham
Role: PRINCIPAL_INVESTIGATOR
Newcastle upon Tyne Hospiatls NHS Foundation Trust
Locations
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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
Countries
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Related Links
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British Society for Paediatric Endocrinology and Diabetes supports this study
Other Identifiers
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NUTH 2759
Identifier Type: -
Identifier Source: org_study_id
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