A pilot randomized trial of adjuvant rituximab or placebo for nonsplenectomized patients with immune thrombocytopenia

被引:94
作者
Arnold, Donald M. [1 ,2 ]
Heddle, Nancy M. [1 ]
Carruthers, Julie [1 ]
Cook, Deborah J. [1 ]
Crowther, Mark A. [1 ]
Meyer, Ralph M. [3 ,4 ,5 ,6 ]
Liu, Yang [1 ]
Cook, Richard J. [1 ,7 ]
McLeod, Anne [8 ]
MacEachern, Janet A. [9 ]
Mangel, Joy [10 ]
Anderson, David [11 ]
Vickars, Linda [12 ]
Tinmouth, Alan [13 ,14 ]
Schuh, Andre C. [15 ]
Kelton, John G. [1 ]
机构
[1] McMaster Univ, Dept Med, Michael G DeGroote Sch Med, Hamilton, ON, Canada
[2] Canadian Blood Serv, Hamilton, ON, Canada
[3] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada
[4] Queens Univ, Dept Oncol, Kingston, ON, Canada
[5] Queens Univ, Dept Med, Kingston, ON K7L 3N6, Canada
[6] Queens Univ, Dept Community Hlth & Epidemiol, Kingston, ON K7L 3N6, Canada
[7] Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada
[8] Univ Toronto, Dept Med, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada
[9] Grand River Hosp, Dept Oncol, Grand River Reg Canc Ctr, Kitchener, ON, Canada
[10] Univ Western Ontario, Dept Med, Div Hematol, London, ON, Canada
[11] Dalhousie Univ, Dept Med, Halifax, NS, Canada
[12] Univ British Columbia, Dept Med, Vancouver, BC, Canada
[13] Ottawa Hosp, Dept Med, Ottawa, ON, Canada
[14] Ottawa Hosp, Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada
[15] Univ Toronto, Dept Med, Univ Hlth Network, Toronto, ON, Canada
关键词
PURPURA; ADULTS; EFFICACY; SAFETY; CHILDREN; THERAPY;
D O I
10.1182/blood-2011-08-374777
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The benefit of adding rituximab to standard treatment in nonsplenectomized patients with primary immune thrombocytopenia (ITP) is uncertain. We performed a pilot randomized trial to determine the feasibility of recruitment, protocol adherence, and blinding of a larger trial of rituximab versus placebo; and to evaluate the potential efficacy of adjuvant rituximab in ITP. Nonsplenectomized adults with newly diagnosed or relapsed ITP who were receiving standard ITP therapy for a platelet count below 30 x 10(9)/L were randomly allocated to receive 4 weekly infusions of 375 mg/m(2) rituximab or saline placebo. Sixty patients were recruited over 46 months, which was slower than anticipated. Protocol adherence and follow-up targets were achieved, and blinding was successful for research staff but not for patients. After 6 months, there was no difference between rituximab and placebo groups for the composite outcome of any platelet count below 50 x 10(9)/L, significant bleeding or rescue treatment once standard treatment was stopped (21/32 [65.6%] vs 21/26 [80.8%]; relative risk = 0.81, 95% confidence intervals, 0.59%-1.11%). Timely accrual poses a challenge to the conduct of a large randomized trial of rituximab for presplenectomy ITP. No difference in the frequency of the composite outcome was observed in this pilot trial (registered at www.clinicaltrials.gov NCT00372892). (Blood. 2012; 119(6): 1356-1362)
引用
收藏
页码:1356 / 1362
页数:7
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