Mixed cryoglobulinemia HCV- related or unrelated Haematological Disorders Cryoglobulinaemia
Conditions
Interventions
NON-Rituximab (RTX) GROUP (conventional treatment, i.e., as chosen by the expert clinician in that individual patient among the following):
1. Glucocorticoids (maximal initial dose of 1 mg/kg/day of
if response was observed, azathioprine or cyclophosphamide might be suspended after the end of month +6 after randomization, and then reintroduced if clinical relapse occurred (as it occurs in the cur
if response was observed, plasmapheresis could be suspended after the end of month +6 after randomization, and then reintroduced if clinical relapse occurred (current clinical practice). At least two
if introduced with RTX, only low doses (= 0.1 mg/kg/day of prednisone equivalents) were allowed. In case of clinical disease relapse in this Group, retreatment with RTX, at the same schedule, was perm
Sponsors
University of Udine (Italy)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with CV with type II cryoglobulins 2. HCV? related or unrelated, classified according to published criteria 3. With positive serum cryoglobulins 4. Suffered from severe active CV manifestations, i.e., skin ulcers, active glomerulonephritis, or worsening or refractory peripheral neuropathy 5. In patients with HCV-related CV, study inclusion implied that antiviral therapy with interferon plus ribavirin had failed, had been poorly tolerated, or was considered contraindicated 6. Patients aged 18-80 years 7. Negative for antibodies against the human immunodeficiency virus (HIV), hepatitis B virus core antigen, and for hepatitis B virus surface antigen
Exclusion criteria
Exclusion criteria: 1. Active CV manifestations with immediate risk for patient survival 2. Acute renal failure or rapidly progressive glomerulonephritis 3. Severe concomitant uncontrolled illness CV-unrelated 4. Active or recurrent infections 5. History of cancer (except for CV-related indolent B-cell lymphoproliferation in the bone marrow, not requiring treatment) 6. Alcohol or drug abuse 7. Serum creatinin > 4 mg/dl 8. AST or ALT > 3 times the upper limit of normal 9. Haemoglobin < 8 g/dl 10. Neutrophils < 1000/mmc or total leukocytes < 1500/mmc 11. Platelets < 40.000/mmc 12. History of severe allergic reactions to monoclonal antibodies 13. Pregnancy (if reproductive potential, an accepted birth control method was required) 14. Previous treatment with RTX 15. Previous failure of all the following: 15.1. High dose glucocorticoids 15.2. Plasma exchange 15.3. Cyclophosphamide 15.4. Azathioprine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients surviving on treatment at the end and 12 months after randomization, i.e., after a follow-up considered sufficient to assess both the efficacy and safety of treatment. Efficacy and safety issues were in fact considered equally relevant in the long term, and a single end point integrating both of them was then chosen. Survival of treatment was statistically higher in RTX Group in comparison to non-RTX Group (conventional treatment). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The proportion of patients surviving on treatment at the end month +24, i.e., to evaluate the long-term efficacy and safety of treatment 2. The proportion of patients surviving on treatment at the end month +6, i.e., to evaluate the short-term efficacy and safety of treatment 3. The proportion of patients surviving on treatment at the end month +3, i.e., to evaluate the very early efficacy and safety of treatment 4. Superiority of RTX to decrease the global disease activity, as defined by the Birmingham Vasculitis Activity Score (BVAS) 5. Superiority of RTX for response in the single CV manifestations considered in the randomization scheme. 6. Efficacy of RTX in patients where conventional treatment had failed 7. Duration of response to RTX and efficacy of retreatment 8. Assessment of the profile of side effects of RTX, both in the short and the long term | — |
Countries
Italy
Outcome results
None listed