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

Phase 3

Completed

• Conditions: ANCA-associated Primary Necrotizing Vasculitides
• Interventions: Drug: Placebo; Drug: Rosuvastatin

• Registration Number: NCT02117453
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

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 Timeline

• Study First Submitted: 2014-04-16
• Study First Submitted QC: 2014-04-18
• Study First Posted: 2014-04-21
• Study Start: 2014-10-27
• Primary Completion: 2019-11-07
• Study Completion: 2019-11-07
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-10
• Last Update Posted: 2022-10-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 121

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 to the 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group II	Placebo	Placebo
Group I	Rosuvastatin	Rosuvastatin 20 mg/day

Primary Outcome Measures

Name	Time	Method
Mean change from baseline in mean carotid intima-media thickness for 2 predefined sites (distal common carotid arteries)	24 months	Assessed with B-mode ultrasound

Secondary Outcome Measures

Name	Time	Method
Mean change from baseline in serum biomarkers of subclinical atherosclerosis at 6, 12 and 24 months	24 months	ultra-sensitive CRP, VCAM-1, P-selectin, thrombomodulin
Rate of vasculitis relapses defined by BVAS>0	24 months
Mean change from baseline in lipid profile (triglycerids, total, HDL and LDL cholesterol) at 6, 12 and 24 months compared to baseline value.	24 months
Annualized rate of change in mean carotid intima-media thickness for 2 predefined sites (distal common carotid arteries)	24 months	Assessed with B-mode ultrasound
Mean change from baseline in the number of plaques in three peripheral vessels (carotid and femoral arteries and abdominal aorta) at 6, 12 and 24 months	24 months	Assessed with B-mode ultrasound
Rate of major cardiovascular events (myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes)	24 months
Rate of adverse events	24 months

Trial Locations

Locations (1)

Hopital Cochin; 🇫🇷 Paris, France