Block-replacement Therapy During Radioiodine Therapy

NCT ID: NCT00150124

Last Updated: 2013-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2009-03-31

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.

Conditions

Toxic Nodular Goitre; Graves' Disease

Keywords

Radioiodine therapy; Graves' disease; toxic nodular goiter; antithyroid drugs; levothyroxine; radioprotection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

block-replacement therapy

BRT regimen until 3 months after 131I therapy

Group Type: EXPERIMENTAL

MTZ+LT4

Intervention Type: DRUG

methimazole

methimazole stopped 8 days before 131I therapy

Group Type: ACTIVE_COMPARATOR

Methimazole

Intervention Type: DRUG

Interventions

MTZ+LT4

Intervention Type: DRUG

Methimazole

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Steen Bonnema

OTHER

Sponsor Role: lead

Responsible Party

Steen Bonnema

Consultant, phd, DMSc

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Steen J. Bonnema, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Locations

Department of Endocrinology, Odense University Hospital

Odense, Funen, Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 21175612 (View on PubMed)

Other Identifiers

012

Identifier Type: -

Identifier Source: org_study_id