Clinical trial NCT02117453: Multicenter, Prospective, Randomized, Controlled, Double-blind Trial on the Impact of Rosuvastatin on Subclinical Markers of Atherosclerosis in Patients With Primary Necrotizing Vasculitides
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ANCA-associated Primary Necrotizing Vasculitides
Keywords: ANCA vasculitis
Statin
Subclinical markers of atherosclerosis
Cardiovascular events
Myocardial infarction
Stroke
Arterial revascularization
Unstable angina
Death
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2014-04-21
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean change from baseline in mean carotid intima-media thickness for 2 predefined sites (distal common carotid arteries)
timeFrame: 24 months
Secondary outcomes:
measure: Annualized rate of change in mean carotid intima-media thickness for 2 predefined sites (distal common carotid arteries)
timeFrame: 24 months
measure: 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
timeFrame: 24 months
measure: Mean change from baseline in serum biomarkers of subclinical atherosclerosis at 6, 12 and 24 months
timeFrame: 24 months
measure: Rate of major cardiovascular events (myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes)
timeFrame: 24 months
measure: Rate of vasculitis relapses defined by BVAS>0
timeFrame: 24 months
measure: Rate of adverse events
timeFrame: 24 months
measure: Mean change from baseline in lipid profile (triglycerids, total, HDL and LDL cholesterol) at 6, 12 and 24 months compared to baseline value.
timeFrame: 24 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Cochin
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Benjamin Terrier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Loic Guillevin, MD, PhD
role: STUDY_CHAIR
References: