Sabry S. Ayad MD , Thomas Beaver MD , David Corteville MD , Madhav Swaminathan MD , Ronald G. Pearl MD , Shakil Aslam MD , Philipp Andreas Csomor PhD , Gabriela Alperovich MD , John Neylan MD
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Secondary end points included the proportions of patients who developed major adverse kidney events by day 30 or 90 and the percentage of patients diagnosed with AKI through day 5.</div></div><div><h3>Results</h3><div>In total, 259 patients received study treatment (ANG-3777, n = 129; placebo, n = 130). Through day 6, there was no significant difference in least-squares mean change in serum creatinine between ANG-3777 and placebo (1.1%; 95% confidence interval, −6.2 to 8.4; <em>P</em> = .77), or in proportions of patients who developed major adverse kidney events by day 30 (18.6% vs 16.2%; <em>P</em> = .60) or day 90 (14.7% vs 21.5%; <em>P</em> = .16). Similar proportions of patients were diagnosed with AKI through day 5 (ANG-3777, 47.3%; placebo, 48.5%); however, exploratory analysis revealed more patients diagnosed with AKI postoperatively showed signs of recovery after treatment with ANG-3777 than placebo. 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引用次数: 0
摘要
目的研究肝细胞生长因子模拟物 ANG-3777 在减轻接受心肺旁路手术的患者急性肾损伤(AKI)风险方面的安全性和有效性:在这项双盲安慰剂对照研究(GUARD)中,患者被随机分配接受静脉注射 ANG-3777 2 mg/kg 或安慰剂,每天一次,连续 4 天。主要终点是 AKI 严重程度,以第 2 到第 6 天血清肌酐升高百分比浓度-时间曲线下的平均面积来衡量。次要终点包括第30天或第90天出现主要肾脏不良事件的患者比例,以及第5天确诊为AKI的患者比例:共有 259 名患者接受了研究治疗(ANG-3777,129 人;安慰剂,130 人)。到第 6 天,ANG-3777 和安慰剂的血清肌酐最小二乘法平均值变化无显著差异(1.1%;95% CI,-6.2,8.4;P = .77),第 30 天(18.6% vs 16.2%;P = .60)或第 90 天(14.7% vs 21.5%;P = .16)发生重大肾脏不良事件的患者比例也无显著差异。第 5 天确诊为 AKI 的患者比例相似(ANG-3777,47.3%;安慰剂,48.5%);但是,探索性分析显示,术后确诊为 AKI 的患者在接受 ANG-3777 治疗后出现恢复迹象的人数多于安慰剂。总体而言,ANG-3777的耐受性良好,各治疗组的治疗突发不良事件发生率相似:本研究结果不支持 ANG-3777 在预防心肺旁路术后发生 AKI 方面的疗效。
Development of and recovery from acute kidney injury after cardiac surgery: Randomized phase 2 trial of the hepatocyte growth factor mimetic ANG-3777
Objectives
To investigate the safety and efficacy of ANG-3777, a hepatocyte growth factor mimetic, in mitigating the risk of acute kidney injury (AKI) in patients undergoing cardiac surgery with cardiopulmonary bypass.
Methods
In this double-blind placebo-controlled study (Guard Against Renal Damage [GUARD]), patients were randomized to receive intravenous ANG-3777 2 mg/kg or placebo once daily for 4 days. The primary end point was severity of AKI, measured by mean area under the concentration-time curve on percent increase in serum creatinine from days 2 to 6. Secondary end points included the proportions of patients who developed major adverse kidney events by day 30 or 90 and the percentage of patients diagnosed with AKI through day 5.
Results
In total, 259 patients received study treatment (ANG-3777, n = 129; placebo, n = 130). Through day 6, there was no significant difference in least-squares mean change in serum creatinine between ANG-3777 and placebo (1.1%; 95% confidence interval, −6.2 to 8.4; P = .77), or in proportions of patients who developed major adverse kidney events by day 30 (18.6% vs 16.2%; P = .60) or day 90 (14.7% vs 21.5%; P = .16). Similar proportions of patients were diagnosed with AKI through day 5 (ANG-3777, 47.3%; placebo, 48.5%); however, exploratory analysis revealed more patients diagnosed with AKI postoperatively showed signs of recovery after treatment with ANG-3777 than placebo. Overall, ANG-3777 was well tolerated, with similar incidences of treatment-emergent adverse events between treatment arms.
Conclusions
Findings from this study do not support the efficacy of ANG-3777 in preventing the development of AKI after cardiopulmonary bypass.
期刊介绍:
The Journal of Thoracic and Cardiovascular Surgery presents original, peer-reviewed articles on diseases of the heart, great vessels, lungs and thorax with emphasis on surgical interventions. An official publication of The American Association for Thoracic Surgery and The Western Thoracic Surgical Association, the Journal focuses on techniques and developments in acquired cardiac surgery, congenital cardiac repair, thoracic procedures, heart and lung transplantation, mechanical circulatory support and other procedures.