A Trial to Evaluate the Efficacy of Orbital Radiotherapy in Graves' Orbitopathy

Официальное название

A Phase IV, Randomized, Multi-center Clinical Trial to Compare the Efficacy of Orbital Radiotherapy in Association With Intravenous Glucocorticoids vs Intravenous Glucocorticoids Alone for Moderately Severe and Active Graves' Orbitopathy

Обзор

Graves' orbitopathy (GO) is a disfiguring and disabling disease that profoundly impairs the quality of life of affected patients. High dose intravenous (iv) glucocorticoids (GC) (ivGC) is a well established, widely used treatment for active GO. The use of systemic glucocorticoids takes advantage from their immune suppressive and antiinflammatory actions, resulting in an overall beneficial effect ranging from \~35 to \~60% of patients in various studies. The intravenous route of administration has been shown to be superior to the oral route, both in terms of GO outcome and side effect profile. The combination of ivGC and orbital radiotherapy (OR) is used routinely in patients with moderate-severe, active GO, as a second-line treatment, as also recommended in the recent Guidelines published by the European Thyroid Association/European Group on Graves' Orbitopathy. Thus, the majority of studies have shown that OR increases the response rate to GC. Those studies were performed using oral GC, whereas it is not known whether OR potentiate also the effects of ivGC. The present study is aimed at determining whether OR potentiate the effects of ivGC in the treatment of moderately severe and active GO, in terms of GO outcome and quality of life. A possible extension of the study can be foreseen, aimed at investigating the very long time GO outcome.

Вмешательства

• Лучевая терапия Orbital radiotherapy
  A high-voltage linear accelerator will be used and a cumulative radiation dose of 20 Gy will be delivered to each eye in 10 fractionated doses over a period of 2 weeks. All patients will be treated in both eyes.
• Препарат Methylprednisolone
  Methylprednisolone pulse therapy for 12 weeks as follows: 500 mg IV once weekly for 6 weeks, then 250 mg IV once weekly for a further 6 weeks. Cumulative dose 4.5 g.

Первичные конечные точки

• Comparison of overall GO outcome determined using a composite evaluation [Срок оценки: 52 weeks]

Вторичные конечные точки (4)

• Comparison of overall GO outcome determined using a composite evaluation [Срок оценки: 26 weeks]
• Comparison of a disease specific quality of life questionnaire (GO-QoL) [Срок оценки: 26 weeks]
• GO relapse [Срок оценки: 52 weeks]
• Comparison of a disease specific quality of life questionnaire (GO-QoL) [Срок оценки: 52 weeks]

Критерии участия

Критерии включения

• A diagnosis of Graves' disease based on the presence of hyperthyroidism (either untreated or treated with antithyroid drugs) associated with detectable anti-TSH receptor autoantibodies
• No major treatments for hyperthyroidism (thyroidectomy or radioiodine) in the last 3 months
• Euthyroidism on anti-thyroid medications or L'thyroxine (LT4) since at least 2 months
• GO symptoms lasting since no more than one year
• Active GO: CAS ≥ 3 out of 7 (worst eye)
• Moderate or moderately severe GO: at least one of the following signs (worst eye):

• Exophthalmos ≥ 22 mm
• Eye muscle involvement with mono-ocular ductions in any direction of gaze of less than 30° or evident dismotility
• Diplopia according to Gorman score of grades a-c
• No corticosteroids or immunosuppressive treatment for GO in the last 3 months
• No contraindication to OR: diabetes, hypertension, retinopathy of any type, glaucoma
• Male and female patients of age: 35-75 years
• Effective method of contraception during the whole trial and at least six weeks after last intake of trial drugs (only female of reproducing age)
• No mental illness that prevent patients from comprehensive, written informed consent
• Compliant patient, regular follow-up possible

Критерии исключения

• Absence of Graves' hyperthyroidism (present or past)
• Thyroidectomy or radioiodine in the last 3 months
• Uncontrolled hyperthyroidism or hypothyroidism
• GO symptoms lasting since more than one year
• CAS <3 (worst eye)
• Optic neuropathy
• Contraindications to OR (diabetes, retinopathy of any kind)
• Pregnancy, breast-feeding women
• No informed consent
• Acute or chronic liver disease
• Relevant Malignancy
• Chronic renal failure or other diseases of any relevance to prevent steroid treatment 13) Corticosteroids or other immunosuppressive agents within last 3 months
• Recent (≤1 year) history of alcoholism or drug abuse
• Previous orbital disease other than GO, eye injuries or surgery

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT03098225 · ORGO

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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