Antithyroid Drug Treatment of Thyrotoxicosis in Young People
A Randomised Study of Two Anti-thyroid Drug Treatment Regimens in Young People
1 other identifier
interventional
81
1 country
18
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jul 2004
Longer than P75 for phase_3
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2004
CompletedFirst Submitted
Initial submission to the registry
August 18, 2011
CompletedFirst Posted
Study publicly available on registry
September 20, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2015
CompletedSeptember 21, 2016
September 1, 2016
10.4 years
August 18, 2011
September 20, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Biochemical control as reflected by the stability of blood thyroid stimulating hormone (TSH) concentrations
For each patient, TSH will be determined at each visit: the primary outcome variable is obtained by measuring the proportion of TSH concentrations that are outwith the laboratory normal range (in calculating this value, determinations made within six months of diagnosis are ignored).
2.5 years
Secondary Outcomes (3)
Remission rates as defined by patients who are biochemically euthyroid at the end of the 4 year study period.
4 years
The frequency of adverse events on the 2 treatment regimens.
3 years
Additional measures of biochemical control.
3 years
Study Arms (2)
Block and Replace
ACTIVE COMPARATORCarbimazole 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.
Dose Titration
ACTIVE COMPARATORCarbimazole 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.
Interventions
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.
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 5mg and 20 mg tablets Administered as a once or twice daily regimen with total daily dose adjusted according to prevailing biochemistry
50 mg tablets administered once daily with the dose adjusted according to the prevailing biochemistry
25mcg, 50mcg and 100mcg tabletes administered once daily with the dose adjusted according to the prevailing biochemistry
Eligibility Criteria
You may qualify if:
- 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).
- Child has consented/assented or consent via parent/guardian has been gained prior to any study specific procedures
You may not qualify if:
- Known toxic adenoma / toxic hyperplasia (germline activating TSHR mutation).
- McCune Albright Syndrome.
- Previous episodes of Thyrotoxicosis..
- Known allergic response to any of the study medication or ingredients as per SmPC.
- Previous participation in this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
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
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Tim Cheetham
Newcastle upon Tyne Hospiatls NHS Foundation Trust
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr Tim Cheetham
Study Record Dates
First Submitted
August 18, 2011
First Posted
September 20, 2011
Study Start
July 1, 2004
Primary Completion
December 1, 2014
Study Completion
November 1, 2015
Last Updated
September 21, 2016
Record last verified: 2016-09