Direct Antiviral Agents for Hepatitis C Virus-associated Cryoglobulinaemia Vasculitis

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Unknown status

CT.gov ID

NCT02856243

Collaborator

(none)

120

Enrollment

Location

Study Details

Study Description

Brief Summary

Cryoglobulinemia are responsible for systemic vasculitis, and the most frequently targeted organs are the skin, joints, kidney and peripheral nervous system. Cryoglobulinemia vasculitides are associated with significant morbidity and mortality, and require therapeutic intervention. With the discovery of hepatitis C virus (HCV) as the etiologic agent for most cases of mixed cryoglobulinemia new opportunities and problems for crafting therapy of HCV mixed cryoglobulinemia (MC) have emerged. A new and major concern was the potential adverse effects that immunosuppressive therapy with glucocorticoids and cytotoxic drugs could have on an underlying chronic viral infection. Alternatively the discovery of HCV provided the opportunity to control HCV-MC with antiviral therapy based on the belief that the underlying infection was driving immune complex formation and resultant vasculitis. Inducing a sustained virologic and clinical response and minimizing the use of immunosuppressive drugs are the main goals in the treatment of patients with HCV-MC vasculitis. Aggressive antiviral therapy has been shown to induce a complete remission of HCV-MC in up to 70% of patients. New antiviral combination, Interferon (IFN)-free regimens have recently proved very high virological response rate and with a very good safety profile and now need to be evaluated in severe and/or refractory HCV-MC patient's population.

Condition or Disease	Intervention/Treatment	Phase
Vasculitis Cryoglobulinemia Hepatitis C	Drug: new antiviral therapy

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Direct Antiviral Agents for Hepatitis C Virus-associated Cryoglobulinaemia Vasculitis

Study Start Date :

Nov 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2016

Outcome Measures

Primary Outcome Measures

Number of participants with complete clinical response of cryoglobulinaemia vasculitis [At week 24]
The complete clinical response is defined by improvement of all the affected organs involved at baseline and the absence of clinical relapse. The skin and articular improvement will be evaluated clinically (i.e. disappearance of purpura and/or ulcers and/or skin necrosis, disappearance of arthralgia and/or arthritis). Renal improvement will be evaluated biologically (i.e. proteinuria <0.3g/24h, disappearance of hematuria and improvement of Glomerular filtration rate (GFR) > 20% at week 24 if GFR < 60 ml/min/1.73 m² at diagnosis). Peripheral neurological improvement will be evaluated clinically (i.e. improvement of pains and paraesthesia by visual analogue scales, improvement of muscular testing in case of motor impairment at baseline) and/or electrophysiologically (i.e. improvement of electromyogram abnormalities at week 24 compared to baseline). The neuropathy total symptom score-6 (NTSS-6) will be applied to evaluate individual neuropathy sensory symptoms.

Secondary Outcome Measures

Number of participants with sustained virological response [At week 36]
A sustained virological response is defined by the absence of detectable serum HCV RNA twelve weeks after the end of antiviral therapy
Number of participants with Immunological complete response [At week 36]
Immunological complete response is defined by negativation of cryoglobulin at week 36.
rate of side effects [up to week 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

at least 18 years of age or older
present an active HCV vasculitis defined by a clinically active vasculitis with skin, joint, renal, peripheral nerve, central neurological, digestive, pulmonary and/or cardiac involvement (no histological evidence needed if patient had purpura)
chronic active HCV infection (positive HCV RNA)
informed consent