DELP治疗急性脑梗死多中心随机对照试验的初步分析

目的:评价体外血浆脂蛋白过滤器(DELP)治疗急性脑梗死的有效性与安全性。方法:采用多中心、随机、基础治疗平行对照试验设计,90例发病<48h的脑梗死患者随机分为治疗组55例、对照组35例,经DELP治疗后4d、14d以NIHSS量表评定神经功能缺损程度,BI量表评定日常生活能力,治疗后90d随访所有患者的改良Rankin评分(mRS)。结果:治疗后14d治疗组NIHSS降低趋势明显优于对照组(P<0.01),但BI的变化无差异;治疗后90d治疗组mRS良好预后的患者比例显著高于对照组(P<0.01);治疗后4d各项指标间2组之间差异显著(P<0.01),治疗14d后则恢复治疗前水平。共发生不良事件11例次,2组之间无显著性差异。结论:DELP促进急性脑梗死神经功能早期恢复,明显改善患者的良好预后比例,减低了严重残疾的预后。     

Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III,Randomized, Double-blind,Noninferiority Clinical Trial

PurposeThe purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC).MethodsThis Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m² 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements.FindingsA total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46–1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55–1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm.ImplicationsThe proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.