Direct Antiviral Agents for Hepatitis C Virus-associated Cryoglobulinaemia Vasculitis

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.

Study Overview

• Status: Unknown
• Conditions: Vasculitis; Hepatitis C; Cryoglobulinemia
• Intervention / Treatment: Drug: new antiviral therapy

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Hôpital La Pitié Salpêtrière

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

To be eligible, the patient must have been at least 18 years of age or older, without any upper age limit, informed and 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), and a chronic active HCV infection (positive HCV RNA).

Description

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

Exclusion Criteria:

• non-active cryoglobulinaemia vasculitis
• HIV
• active hepatitis B virus (HBV) infection
• current decompensated cirrhosis.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with complete clinical response of cryoglobulinaemia vasculitis	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.	At week 24

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: July 31, 2016
• First Posted (Estimate): August 4, 2016

Study Record Updates

• Last Update Posted (Estimate): September 29, 2016
• Last Update Submitted That Met QC Criteria: September 28, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Immune System Diseases; Immunoproliferative Disorders; Hematologic Diseases; Liver Diseases; Hemorrhagic Disorders; Flaviviridae Infections; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Vasculitis; Cryoglobulinemia; Anti-Infective Agents; Antiviral Agents
• Other Study ID Numbers: VASCUVALDIC 2 study