Comparing treatments for hyperthyroidism in patients with Graves' orbitopathy

A Phase III, Randomized, Controlled, Open Label, no Profit, Single-center Intervention Study to Compare the Effect of a Conservative (Antithyroid Drugs) and an Ablative Approach (Radioiodine or Total Thyroidectomy) for the Treatment of Hyperthyroidism in Patients With Graves' Disease and Moderate-to-severe and Active Graves' Orbitopathy (GO) Treated With Intravenous Glucocorticoids (ABLAGO Study)

This study is testing whether treating hyperthyroidism with medication or surgery helps people with Graves' disease and eye problems feel better and prevents their eye issues from getting worse.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: University of Pisa (other)
• Locations: 1 site (Pisa, PI)
• Trial ID: NCT04776993 on ClinicalTrials.gov

What this trial studies

This study compares two treatment approaches for hyperthyroidism in patients with Graves' disease and moderate-to-severe Graves' orbitopathy. One group will receive a conservative treatment using antithyroid drugs, while the other group will undergo an ablative treatment using radioactive iodine or total thyroidectomy. The goal is to determine which approach better protects against the progression of Graves' orbitopathy. All patients will also receive intravenous glucocorticoids during the trial.

Who should consider this trial

Good fit: Ideal candidates are patients diagnosed with Graves' disease who have moderate-to-severe and active Graves' orbitopathy.

Not a fit: Patients with a duration of Graves' disease longer than 18 months or those with mild or inactive Graves' orbitopathy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could identify the most effective treatment approach for managing hyperthyroidism in patients with Graves' orbitopathy, potentially improving patient outcomes.

How similar studies have performed: While there have been studies on treatments for Graves' disease, this specific comparison of conservative versus ablative approaches in the context of Graves' orbitopathy is novel.

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

Where this trial is running

Pisa, PI

• Endocrinology Unit II — Pisa, PI, Italy (RECRUITING)

Study contacts

• Study coordinator: Michele Marino

Conditions: Graves' Orbitopathy