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

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.

Study Overview

• Status: Completed
• Conditions: ANCA-associated Primary Necrotizing Vasculitides
• Intervention / Treatment: Drug: Placebo; Drug: Rosuvastatin

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 Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Hôpital Cochin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group I; Rosuvastatin 20 mg/day	Drug: Rosuvastatin; Rosuvastatin 20 mg/day
PLACEBO_COMPARATOR: Group II; Placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of adverse events		24 months
Annualized rate of change in mean carotid intima-media thickness for 2 predefined sites (distal common carotid arteries)	Assessed with B-mode ultrasound	24 months
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	Assessed with B-mode ultrasound	24 months
Mean change from baseline in serum biomarkers of subclinical atherosclerosis at 6, 12 and 24 months	ultra-sensitive CRP, VCAM-1, P-selectin, thrombomodulin	24 months
Rate of major cardiovascular events (myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes)		24 months
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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Loic Guillevin, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 27, 2014
• Primary Completion (ACTUAL): November 7, 2019
• Study Completion (ACTUAL): November 7, 2019

Study Registration Dates

• First Submitted: April 16, 2014
• First Submitted That Met QC Criteria: April 18, 2014
• First Posted (ESTIMATE): April 21, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Stroke; Myocardial infarction; Statin; Unstable angina; Death; Cardiovascular events; ANCA vasculitis; Subclinical markers of atherosclerosis; Arterial revascularization
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Vasculitis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: P120127; 2013-002531-15 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO