Direct Antiviral Agents for Hepatitis C Virus-associated Cryoglobulinaemia Vasculitis

• ClinicalTrials.gov Identifier: NCT02856243
• Recruitment Status: Unknown
• First Posted: August 4, 2016
• Last Update Posted: September 29, 2016
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

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
Vasculitis; Cryoglobulinemia; Hepatitis C	Drug: new antiviral therapy

Study Design

• Study Type: Observational
• Estimated Enrollment: 120 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Direct Antiviral Agents for Hepatitis C Virus-associated Cryoglobulinaemia Vasculitis
• Study Start Date: November 2013
• Estimated Primary Completion Date: December 2016

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Number of participants with complete clinical response of cryoglobulinaemia vasculitis [ Time Frame: 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 :

1. Number of participants with sustained virological response [ Time Frame: 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
2. Number of participants with Immunological complete response [ Time Frame: At week 36 ]
   Immunological complete response is defined by negativation of cryoglobulin at week 36.
3. rate of side effects [ Time Frame: up to week 24 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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).

Criteria

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.

Contacts and Locations

Contacts

Contact: David Saadoun, MD PHD; 142178009 ext +33; david.saadoun@aphp.fr

Locations

France

hopital La pitié Salpétrière; Recruiting

Paris, France, 75013

Contact: david saadoun, MD phd 142178009 ext +33 david.saadoun@aphp.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02856243
• Other Study ID Numbers: VASCUVALDIC 2 study
• First Posted: August 4, 2016
• Last Update Posted: September 29, 2016
• Last Verified: July 2016

Additional relevant MeSH terms:

Hepatitis A; Hepatitis C; Hepatitis; Vasculitis; Cryoglobulinemia; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Vascular Diseases; Cardiovascular Diseases; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Immunoproliferative Disorders; Immune System Diseases; Antiviral Agents; Anti-Infective Agents