A Conservative vs an Ablative Approach for Treatment of Hyperthyroidism in Patients With Graves' Orbitopathy

NCT ID: NCT04776993

Last Updated: 2023-03-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-02
• Study Completion Date: 2026-03-01

Brief Summary

Graves' disease (GD) is the most frequent cause of hyperthyroidism in iodine sufficient countries and Graves' orbitopathy (GO) is its most common extrathyroidal manifestation. Restoration and maintenance of euthyroidism are imperative in Graves' disease patients with GO. The main treatment options for Graves' hyperthyroidism are antithyroid drugs, radioactive iodine (RAI), and surgery. Whether one or the other therapy for Graves' hyperthyroidism offers the best protection against GO is not established. The study is aimed at comparing the effects of a conservative approach (antithyroid drugs, ATDs, experimental arm) vs an ablative approach (radioiodine or total thyroidectomy) of thyroid treatment on the overall outcome of GO in patients with GD and moderate-to-severe and active GO treated with intravenous glucocorticoids.

Conditions

Graves' Orbitopathy

Study Design

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

Study Groups

Methimazole

Antithyroid drugs (at individualized dosage) for 72 weeks and a cumulative dose of 4.5 g of methylprednisolone divided into 12 weekly infusions

Group Type: EXPERIMENTAL

Methimazole

Intervention Type: DRUG

Methimazole for 72 weeks

Thyroid ablation

Radioiodine therapy or total thyroidectomy (according to ultrasound thyroid volume) and a cumulative dose of 4.5 g of methylprednisolone divided into 12 weekly infusions

Group Type: ACTIVE_COMPARATOR

Radioiodine or thyroidectomy

Intervention Type: PROCEDURE

Treatment with radioiodine or with thyroidectomy

Interventions

Methimazole

Methimazole for 72 weeks

Intervention Type: DRUG

Radioiodine or thyroidectomy

Treatment with radioiodine or with thyroidectomy

Intervention Type: PROCEDURE

Other Intervention Names

MMI; Thyroid ablation

Eligibility Criteria

Inclusion Criteria

1. Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

2. A diagnosis of Graves' disease based on the presence of hyperthyroidism associated with detectable anti-thyrotropic hormone (TSH) receptor autoantibodies (TRAb). Patients must be euthyroid under control on stable medical regimen and every effort will be made to maintain the euthyroid status for the entire duration of the clinical trial.

3. Duration of Graves' disease shorter than 18 months

4. A moderate-to-severe GO, defined as the presence of at least one of the following criteria in the most affected eye: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm

5. Active GO: CAS ≥ 3 out of 7 points in the most affected eye. Taking into account severity (moderate-to-severe) and activity (CAS ≥ 3/7) of GO, patients are eligible for methylprednisolone treatment according to clinical practice.

6. Duration of GO shorter than 18 months

7. Male and female patients of age 18-75 years

8. Compliant patient, regular follow-up possible

Exclusion Criteria

1. Optic neuropathy

2. Previous therapy for Graves' disease with radioiodine or thyroidectomy

3. Corticosteroids or other immunosuppressive treatment for GO or other reasons in the last 3 months.

4. Previous surgical treatment and/or radiotherapy for GO

5. Contraindications to GC: hypersensitivity to the active substance or to any of the excipients; uncontrolled hypertension, uncontrolled diabetes; history of peptic ulcer; urinary infections, glaucoma, systemic fungal infections, systemic infections unless appropriate therapy is employed, idiopathic thrombocytopenic purpura, cerebral edema associated with malaria.

6. Use of medications interfering with GC or increasing the risk of GC-related adverse events (see prohibited therapies)

7. Acute or chronic liver disease

8. Contraindications to ATD: hypersensitivity to the active substance or to any of the excipients; breastfeeding

9. Women of childbearing potential (WOCBP, namely not in menopause or in menopause since less than two years; in all other instances women will be considered as non-WOCBP) and men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (as indicated in Appendix) for at least 6 and 7,5 months, respectively, after the last dose of the investigational drug (see also 2014_09_HMA_CTFG_Contraception.pdf, namely the "2014 CTFG Reccommendtions related to contraception and pregnancy testing in clinical trials")

10. Contraindications of any kind to perform thyroidectomy

11. Mental illness that prevent patients from comprehensive, written informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pisa

OTHER

Sponsor Role: lead

Responsible Party

Marinò Michele

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Endocrinology Unit II

Pisa, PI, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Michele Marino

Role: CONTACT

michele.marino@med.unipi.it

+39050997346

Giulia Lanzolla

Role: CONTACT

giulia.lanzolla8@gmail.com

+39050997346

Facility Contacts

Michele Marinò, MD

Role: primary

michele.marino@med.unipi.it

+39050997346

Giulia Lanzolla, MD

Role: backup

giulia.lanzolla8@gmail.com

+39050997346

Other Identifiers

ABLAGO

Identifier Type: -

Identifier Source: org_study_id