A pilot randomized trial of adjuvant rituximab or placebo for nonsplenectomized patients with immune thrombocytopenia.
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 × 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 × 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).
Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. arnold@mcmaster.ca
Donald M
DM
Arnold
Nancy M
NM
Heddle
Julie
J
Carruthers
Deborah J
DJ
Cook
Mark A
MA
Crowther
Ralph M
RM
Meyer
Yang
Y
Liu
Richard J
RJ
Cook
Anne
A
McLeod
Janet A
JA
MacEachern
Joy
J
Mangel
David
D
Anderson
Linda
L
Vickars
Alan
A
Tinmouth
Andre C
AC
Schuh
John G
JG
Kelton
D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D059352:Musculoskeletal Pain / Q000139:chemically induced; D010865:Pilot Projects; D010919:Placebos; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy*; D000069283:Rituximab; D013156:Splenectomy; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D010919:Placebos; D000069283:Rituximab