Graves' orbitopathy (GO) is the most common extra-thyroidal manifestation of Graves' disease (GD). Based on its clinical signs and symptoms, GO is graded as mild, moderate-to-severe, or severe, and active or inactive, the latter feature being established on a 5/7-scale score named Clinical Activity Score (CAS).
The European Group on Graves Orbitopathy (EUGOGO) has recently formulated and published up-to-date guidelines for the management of GO, according to which high dose intravenous (iv) glucocorticoids (GC) (ivGC) is the first line treatment for moderate-to-severe and active GO. A protective effect of atorvastatin on the development of GO in patients with GD has been reported, based on which we recently conducted a phase II, randomized, open label clinical trial and found that atorvastatin improves the response of GO to ivGCs in hypercholesterolemic patients. The effect was unrelated to cholesterol levels, suggesting that it may be the consequence of a direct action of atorvastatin. To investigate this issue further and to introduce atorvastatin in the clinical practice, we designed the present Phase III, double-blinded, multicenter, randomized, adaptive, superiority, no profit, clinical trial to evaluate the effects of atorvastatin on Graves' Orbitopathy (GO) in patients with moderate-to-severe and active GO subjected to intravenous glucocorticoid therapy, regardless of cholesterol levels.
Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
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
A moderate-to-severe GO, defined as the presence of at least one of the following criteria: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm, lasting since no longer than 9 months
Active GO: CAS (4) ≥ 3 out of 5 points in the most affected eye
Optic neuropathy
Corticosteroids or immunosuppressive treatment for GO in the last 3 months. Use of selenium in the last 3 months or during the clinical trial
Previous surgical or radiant (orbital irradiation) treatment for GO
Radioiodine treatment for hyperthyroidism over the last 3 months, as it can affect GO (4)
Parallel
Atorvastatin 20mg
DrugOne tablet/day, given approximately at 10 pm, after dinner and before going to bed, for 24 weeks
Placebo
Other interventionOne tablet/day, given approximately at 10 pm, after dinner and before going to bed, for 24 weeks
Outcome of GO
Comparison of overall GO outcome determined using a composite evaluation (% of responders). Response is defined as change in two outcome measures in at least one eye, without deterioration in any of the same measures in both eyes (compared to baseline): Patients meeting the improvement criteria will be considered as "responders". All other patients will be considered as "non-responders".
Outcome of GO
Comparison of overall GO outcome determined using a composite evaluation (% of responders). Response is defined as change in two outcome measures in at least one eye, without deterioration in any of the same measures in both eyes (compared to baseline): Patients meeting the improvement criteria will be considered as "responders". All other patients will be considered as "non-responders".
Outcome of GO
Comparison of overall GO outcome determined using a composite evaluation (% of responders). Response is defined as change in two outcome measures in at least one eye, without deterioration in any of the same measures in both eyes (compared to baseline): Patients meeting the improvement criteria will be considered as "responders". All other patients will be considered as "non-responders".
Quality of life (comparison between the two groups)
Quality of life (QoL) will be evaluated using the GO QoL questionnaire (GO-QoL). Questionnaire consists of two subscales: 1) visual functioning (eight questions concerning limitations attributable to decreased visual acuity, diplopia, or both), and 2) appearance (eight questions referring to limitations in psychosocial functioning attributable to changes in appearance). Questions are scored as severely limited (one point), a little limited (two points), or not limited at all (three points). The two scores (8-24 points) are summed into a total score. A higher score means a better QoL. The total score and the subscores will be compared between the two groups
Quality of life (comparison between the two groups)
Quality of life (QoL) will be evaluated using the GO QoL questionnaire (GO-QoL). Questionnaire consists of two subscales: 1) visual functioning (eight questions concerning limitations attributable to decreased visual acuity, diplopia, or both), and 2) appearance (eight questions referring to limitations in psychosocial functioning attributable to changes in appearance). Questions are scored as severely limited (one point), a little limited (two points), or not limited at all (three points). The two scores (8-24 points) are summed into a total score. A higher score means a better QoL. The total score and the subscores will be compared between the two groups
Click on the lead sponsor to view all of their trials.
University of Pisa
Lead sponsor
Università degli Studi dell'Insubria
Collaborator
University of Catania
Collaborator
University of Messina
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
