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Block-replacement Therapy During Radioiodine Therapy

Primary Purpose

Toxic Nodular Goitre, Graves' Disease

Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
MTZ+LT4
Methimazole
Sponsored by
Steen Bonnema
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Toxic Nodular Goitre focused on measuring Radioiodine therapy, Graves' disease, toxic nodular goiter, antithyroid drugs, levothyroxine, radioprotection

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Hyperthyroid patients going to be treated with radioiodine either due to recurrent Graves' disease or toxic nodular goiter. Exclusion Criteria: Age < 18 yrs. Allergy to anti-thyroid drugs Substernal or large (> 100ml) goiter Severe endocrine ophthalmopathy Pregnancy or lactation Suspicion of thyroid malignancy Unsafe contra-conception Physical or mental condition that hinders corporation

Sites / Locations

  • Department of Endocrinology, Odense University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

block-replacement therapy

methimazole

Arm Description

BRT regimen until 3 months after 131I therapy

methimazole stopped 8 days before 131I therapy

Outcomes

Primary Outcome Measures

Thyroid function after one year of follow-up

Secondary Outcome Measures

Thyroid radioiodine 131I uptake
Thyroid volume after one year of follow-up

Full Information

First Posted
September 6, 2005
Last Updated
December 3, 2013
Sponsor
Steen Bonnema
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1. Study Identification

Unique Protocol Identification Number
NCT00150124
Brief Title
Block-replacement Therapy During Radioiodine Therapy
Official Title
The Influence of Continuous Block-replacement Therapy on the Effect of Radioiodine in Patients With Hyperthyroidism
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
January 2003 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Steen Bonnema

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Background: The use of radioactive iodine (131I) therapy as the definite cure of hyperthyroidism is widespread. According to a survey on the management of Graves' disease, thirty per cent of physicians prefer to render their patients euthyroid by antithyroid drugs (ATD) prior to 131I therapy. This strategy is presumably chosen to avoid 131I induced 'thyroid storm', which, however, is rarely encountered. Several studies have consistently shown that patients who are treated with ATD prior to 131I therapy have an increased risk of treatment failure. Mostly, patients with Graves' disease have been studied, while other studies were addressed also toxic nodular goiter. Thus, it is generally accepted that ATD have 'radioprotective' properties, although this view is almost exclusively based on retrospective data and is still under debate. Indeed, this dogma was recently challenged by two randomized trials in Graves' disease, none of which showed such an adverse effect of methimazole pretreatment. It cannot be excluded that the earlier results may have been under influence of selection bias, a source of error almost unavoidable in retrospective studies. Whether ATD is radioprotective also when used in the post 131I period has also been debated. In the early period 131I therapy following a transient rise in the thyroid hormones is seen which may give rise to discomfort in some patients. The continuous use of ATD during 131I therapy, possibly in combination with levothyroxine (BRT: block-replacement therapy), leads to more stable levels of the thyroid hormones. By resuming ATD following 131I therapy, euthyroidism can usually be maintained until the destructive effect of 131I ensues. Nevertheless, many physicians prefer not to resume ATD, probably due to reports supporting that such a strategy reduces the cure rate. Parallel to the issue of ATD pretreatment, the evidence is based on retrospective studies and the ideal set-up should be reconsidered. To underscore the importance of performing randomized trials we showed recently that resumption of methimazole seven days after 131I therapy had no influence on the final outcome. Aim:To clarify by a randomized trial whether BRT during radioiodine therapy of hyperthyroid patients influences the final outcome of this therapy, in a comparison with a regime in which methimazole as mono-therapy is discontinued 8 days before radioiodine. Patients and Methods: Consecutive patients suffering from recurrent Graves' disease (n=50) or a toxic nodular goiter (n=50) are included. All patients are rendered euthyroid by methimazole (MMI) and randomized either to stop MMI eight days before 131I or to be set on BRT. This latter medication continues until three months after 131I. Calculation of the 131I activity (max. 600 MBq) includes an assessment of the 131I half-life and the thyroid volume. Patients are followed for one year with close monitoring of the thyroid function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Toxic Nodular Goitre, Graves' Disease
Keywords
Radioiodine therapy, Graves' disease, toxic nodular goiter, antithyroid drugs, levothyroxine, radioprotection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
block-replacement therapy
Arm Type
Experimental
Arm Description
BRT regimen until 3 months after 131I therapy
Arm Title
methimazole
Arm Type
Active Comparator
Arm Description
methimazole stopped 8 days before 131I therapy
Intervention Type
Drug
Intervention Name(s)
MTZ+LT4
Intervention Type
Drug
Intervention Name(s)
Methimazole
Primary Outcome Measure Information:
Title
Thyroid function after one year of follow-up
Time Frame
one year
Secondary Outcome Measure Information:
Title
Thyroid radioiodine 131I uptake
Time Frame
one month
Title
Thyroid volume after one year of follow-up
Time Frame
one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Hyperthyroid patients going to be treated with radioiodine either due to recurrent Graves' disease or toxic nodular goiter. Exclusion Criteria: Age < 18 yrs. Allergy to anti-thyroid drugs Substernal or large (> 100ml) goiter Severe endocrine ophthalmopathy Pregnancy or lactation Suspicion of thyroid malignancy Unsafe contra-conception Physical or mental condition that hinders corporation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steen J. Bonnema, MD, PhD
Organizational Affiliation
Odense University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Endocrinology, Odense University Hospital
City
Odense
State/Province
Funen
ZIP/Postal Code
5000
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
21175612
Citation
Bonnema SJ, Grupe P, Boel-Jorgensen H, Brix TH, Hegedus L. A randomized trial evaluating a block-replacement regimen during radioiodine therapy. Eur J Clin Invest. 2011 Jul;41(7):693-702. doi: 10.1111/j.1365-2362.2010.02452.x. Epub 2010 Dec 22.
Results Reference
derived

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Block-replacement Therapy During Radioiodine Therapy

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