CYCLOPS
Trial question
What is the role of pulse cyclophosphamide regimen in patients with newly diagnosed generalized ANCA-associated vasculitis with renal involvement?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
41.0% female
59.0% male
N = 149
149 patients (61 female, 88 male).
Inclusion criteria: patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease.
Key exclusion criteria: coexistence of other multisystem autoimmune diseases, HBV, HCV, or HIV infection, serum creatinine level > 500 umol/L, previous cancer; pregnancy; or age < 18 or > 80 years.
Interventions
N=76 pulse cyclophosphamide (intravenous 15 mg/kg every 2-3 weeks plus prednisolone).
N=73 daily oral cyclophosphamide (2 mg/kg per day plus prednisolone).
Primary outcome
Remission at 9 months
88.1%
87.7%
88.1 %
66.1 %
44.0 %
22.0 %
0.0 %
Pulse
cyclophosphamide
Daily oral
cyclophosphamide
No significant
difference ↔
No significant difference in remission at 9 months (88.1% vs. 87.7%; RR 1, 95% CI -2.52 to 4.52).
Secondary outcomes
No significant difference in relapse (13 vs. 6; HR 2.01, 95% CI 0.77 to 5.3).
Significant decrease in absolute cumulative cyclophosphamide dose (8.2 g vs. 15.9 g; HR 0.41, 95% CI 0.23 to 0.71).
Safety outcomes
Significant differences in leukopenia (26% vs. 45%, p = 0.016).
Conclusion
In patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease, pulse cyclophosphamide was not superior to daily oral cyclophosphamide with respect to remission at 9 months.
Reference
de Groot K, Harper L, Jayne DR et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009 May 19;150(10):670-80.
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