The Multicenter Randomized-control Trial of Recombinant Humanized Thrombopietin Treatment in Patients with Idiopathic Thrombocytopenia Purpura

Objective To evaluate the efficacy and safety of recombinant humanized thrombopietin (rhTPO) treatment in patients with idiopathic thrombocytopenia purpura (ITP) who failed to glucocorticosteroids. Methods A multicenter randomized-control study was designed. Patients with ITP who failed to glucocorticosteroids were enrolled and randomized to experimental group (rhTPO+danazol) and control group (danazol). All patients took danazol orally of 0.2 three times per day during the whole trial. Patients in the experimental group were administered subcutaneously with rhTPO 1.0 μg/kg once daily for 14 days and then stopped to observe. Patients in contol group were administered rhTPO as above if their platelet counts were still lower than 20×109/L after 14 days treatment with danazol. Primary endpoints were comparing the mean maximal platelet counts increase and the area under curve (AUC) of the platelet counts during the first phase between two groups. Secondary endpoints were comparing the major response rate (MRR) and total response rate (TRR,including MRR+Good RR) during the first phase,and the platelet counts,MRR,and TRR before and after rhTPO treatment in patients of control group. Results 140 patients were enrolled and randomly assigned 73 patients in experimental group and 67 patients in control group. At the end of study,73 and 63 patients fulfilled FAS,60 and 50 patients fulfilled PPS,respectively in experimental group and control group. Results from FAS and PPS were fully identical. During the first phase,the mean platelet counts increase were 101.2×109/L in experimental group,which was significantly higher than that in control group (33.3×109/L,P=0.0060). The AUC 749.6 of experimental group was significantly higher than 316.2 of control group (P=0.0000). The MRR and TRR were 38.4% and 60.3% respectively,which were significantly higher than that of control group (MRR 7.9%,P=0.0003; TRR 36.5%,P=0.0104). 45 patients whose platelet counts lower than 20×109/L in control group were treated with rhTPO and achieved the MRR 31.1% and TRR 66.7%,which were extremely in accordance with the results of the first phase in experimental group. At day 14 after stopping treatment of rhTPO,the mean platelet counts in experimental group were still around 50×109/L. No influences of rhTPO on white blood count,hemoglobin,bilirubin,clotting tests,anti-GPⅡb/Ⅲa and anti-GPⅠb antibodies were found. The frequencies of adverse events were 34.3% in experimental group and 26.2% in control group,of which abnormal hepatobiliary indices was seen mostly (15.1% in experimental group and 16.9% in control group). Frequency of rhTPO-related adverse events was 13.6%,including mild doss,dizziness,transit defect of vision field,allergic reaction and fatigue. Conclusion rhTPO was well tolerated,and markedly increased platelet counts in patients with chronic ITP. Stimulation of platelet production by rhTPO may provide a new therapeutic option for patients with ITP.