Antithyroid Drug Treatment of Thyrotoxicosis in Young People

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Tim Cheetham, Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01436994
First received: August 18, 2011
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Paediatric Thyrotoxicosis
Procedure: Block and Replace
Procedure: Dose Titration
Drug: carbimazole
Drug: propylthiouracil
Drug: thyroxine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Study of Two Anti-thyroid Drug Treatment Regimens in Young People

Resource links provided by NLM:


Further study details as provided by Newcastle-upon-Tyne Hospitals NHS Trust:

Primary Outcome Measures:
  • Biochemical control as reflected by the stability of blood thyroid stimulating hormone (TSH) concentrations [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Remission rates as defined by patients who are biochemically euthyroid at the end of the 4 year study period. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    To establish whether the remission rates post therapy in young people with thyrotoxicosis are affected by treatment with a 'block and replace' or 'dose titration' regimen. This will be determined by determining the proportion of individuals who are in remission ie who are biochemically euthyroid off ATD-thyroid drug therapy at the end of the of the study period (4 years). The proportion of subjects in remission following block and replace therapy will therefore be compared with the proportion in remission following dose titration.

  • The frequency of adverse events on the 2 treatment regimens. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    This will be reflected by the number of participants with adverse events and by the proportion of patients changing to a different treatment during the study period.

  • Additional measures of biochemical control. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    A comparison of the mean and variability of TSH and thyroid hormone concentrations in the 2 treatment groups.


Estimated Enrollment: 160
Study Start Date: July 2004
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Procedure: 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.
Other Names:
  • Carbimazole
  • propylthiouracil
  • thyroxine
Drug: carbimazole
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
Drug: thyroxine
25mcg, 50mcg and 100mcg tabletes administered once daily with the dose adjusted according to the prevailing biochemistry
Active Comparator: 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.

Procedure: 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.

Other Names:
  • carbimazole
  • propylthiouracil
Drug: carbimazole
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01436994

Locations
United Kingdom
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
Sponsors and Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
Investigators
Principal Investigator: Tim Cheetham Newcastle upon Tyne Hospiatls NHS Foundation Trust
  More Information

Additional Information:
No publications provided

Responsible Party: Tim Cheetham, Dr Tim Cheetham, Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01436994     History of Changes
Other Study ID Numbers: NUTH 2759
Study First Received: August 18, 2011
Last Updated: August 15, 2014
Health Authority: United Kingdom: National Research Ethics Service
United Kingdom: Research & Development Review by Sponsor (Newcastle NHS)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Newcastle-upon-Tyne Hospitals NHS Trust:
thyrotoxic
thyrotoxicosis
paediatric
endocrinology
block and replace
dose titration
carbimazole

Additional relevant MeSH terms:
Thyrotoxicosis
Endocrine System Diseases
Hyperthyroidism
Thyroid Diseases
Carbimazole
Propylthiouracil
Antimetabolites
Antithyroid Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014