Pulse Versus Continuous Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitides
A comparison of intermittent pulsed cyclophosphamide to daily oral cyclophosphamide for the treatment of ANCA-associated systemic vasculitides with kidney involvement.
Performed by the European Vasculitis Study group.
ANCA Associated Systemic Vasculitis
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Trial of Intravenous Pulse Versus Oral Continuous Cyclophosphamide for Induction of Remission in Systemic ANCA-Associated Vasculitides|
- Disease free period, time from remission to relapse or study end.
- Adverse events
- Vasculitis Damage Index
- Cumulative exposure to cyclophosphamide
|Study Start Date:||February 1998|
|Estimated Study Completion Date:||April 2004|
The primary, ANCA-associated systemic vasculitides (AASV), including Wegener’s granulomatosis and microscopic polyangiitis, are progressive, multisystem, autoimmune diseases which respond to immunosuppressive therapy. Their treatment with corticosteroids and cytotoxic drugs has been standardised in a first wave of studies (ECSYSVASTRIAL project), but limitations of such regimens include only partial efficacy and appreciable treatment-related toxicity.
The present trial, CYCLOPS, aims to reduce the cumulative exposure to immunosuppressive drugs by administering cyclophosphamide (CYC) as intermittent pulses. The potential benefit of using CYC in this way for AASV has been demonstrated in preliminary, smaller studies. Patients with previously untreated AASV and, “generalised”, but not life threatening, disease with renal involvement, will be randomised to either continuous oral CYC or intermittent pulse CYC. CYC will be continued until three months after remission has been achieved, with a minimum CYC total duration of six months and maximum duration of twelve months; both limbs will then receive the same maintenance regimen of azathioprine and prednisolone.
The study will last 18 months. The primary end-point is the disease-free period, taken as the period of time from remission until relapse or study end; secondary end-points are adverse effects, cumulative damage and immunosuppressive drug exposure. 160 patients will be required.