STATVAS: Multicenter, Prospective, Randomized, Controlled, Double-blind Trial on the Impact of Rosuvastatin on Subclinical Markers of Atherosclerosis in Patients With Primary Necrotizing Vasculitides

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT02117453

Collaborator

(none)

121

Enrollment

Location

Arms

60.4

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether rosuvastatin could reduce the subclinical markers of atherosclerosis and the incidence of major cardiovascular events in patients with primary necrotizing vasculitides.

Condition or Disease	Intervention/Treatment	Phase
ANCA-associated Primary Necrotizing Vasculitides	Drug: Rosuvastatin Drug: Placebo	Phase 3

Detailed Description

Previous studies demonstrated the presence of subclinical atherosclerosis in patients with ANCA-associated systemic necrotizing vasculitis. Since statins lower levels of inflammatory proteins and cholesterol, we hypothesized that people with ANCA-associated systemic necrotizing vasculitis but without indication for statin treatment according to recommandations might benefit from statin treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

121 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Multicenter, Prospective, Randomized, Controlled, Double-blind Trial on the Impact of Rosuvastatin on Subclinical Markers of Atherosclerosis in Patients With Primary Necrotizing Vasculitides

Actual Study Start Date :

Oct 27, 2014

Actual Primary Completion Date :

Nov 7, 2019

Actual Study Completion Date :

Nov 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group I Rosuvastatin 20 mg/day	Drug: Rosuvastatin Rosuvastatin 20 mg/day
Placebo Comparator: Group II Placebo	Drug: Placebo Placebo

Arm

Intervention/Treatment

Experimental: Group I

Rosuvastatin 20 mg/day

Drug: Rosuvastatin

Rosuvastatin 20 mg/day

Placebo Comparator: Group II

Placebo

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Rate of change in mean carotid intima-media thickness for 6 predefined sites [24 months]
Assessed with B-mode ultrasound

Secondary Outcome Measures

Annualized rate of change in mean carotid intima-media thickness for 6 predefined sites (distal common carotid arteries, carotid bulbs, internal carotid arteries), assessed with B-mode ultrasound [24 months]
Assessed with B-mode ultrasound
Rate of change in the number of plaques in three peripheral vessels (carotid and femoral arteries and abdominal aorta) [24 months]
Assessed with B-mode ultrasound
Rate of change in serum biomarkers of subclinical atherosclerosis [24 months]
ultra-sensitive CRP, VCAM-1, P-selectin, thrombomodulin, circulating endothelial, platelet and leucocytes microparticles
Rate of major cardiovascular events (myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes) [24 months]
Rate of change in vasculitis activity [24 months]
BVAS
Rate of vasculitis relapses [24 months]
Rate of adverse events [24 months]
Rate of change in lipid profile (triglycerids, total, HDL and LDL cholesterol) compared to baseline value. [24 months]
Rate of change in endothelial function with brachial artery flow-mediated dilatation compared to baseline value [24 months]
endothelial function with brachial artery flow-mediated dilatation at months 6, 12 and 24 compared to baseline value, assessed with B-mode ultrasound in a subgroup of 66 patients

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient > 18 years. ANCA-associated vasculitis: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome).

Patients will fulfill the Chapel Hill Consensus Criteria and the American College of Rheumatology criteria, in remission of vasculitis.

Patients in remission of vasculitis after induction therapy (for first flare or relapse), including corticosteroids associated or not with immunosuppressive agents according to Good Clinical Practice for the treatment of vasculitis, between 6 months and 10 years after the beginning of induction therapy.

Patients with informed and signed consent

Exclusion Criteria:

Other systemic vasculitis. Secondary vasculitis (paraneoplastic or infectious). Patient with active vasculitis after induction therapy, requiring salvage therapy.

Inability to sign informed consent. Inability to take the experimental treatment. Hypersensitivity to rosuvastatin or to any of the excipients. Pregnancy. Chronic HCV, HBV and/or HIV infection. Patient receiving other statin or other hypolipemic agent. Patient requiring treatment with statin according to Afssaps recommandations published in 2005 as primary or secondary prevention.

Subclinical atherosclerosis that confers a high cardiovascular risk before patient randomization :

Carotid stenosis greater than 50% in diameter
Ectasia of the abdominal aorta
Intima-media thickening greater than 1.2 mm
Diffuse atherosclerosis lesions
Heterogeneous or hypoechoic prominent plaques greater than 2 mm Participation in another interventional study within 3 months before inclusion. Sick patients will not be excluded if they participate simultaneously in a strictlu observational study or a study with only blood samplings.

Any medical or psycatric disease that could prevent from administrating drugs or from following-up the patient according the to protocol, and/or that would expose the patient to an important number of side effects, according to the principal investigator.

Non affiliation to a social security system or any social protection system.