Verified Hepatorenal Syndrome Reversal As A Robust Multi-Component Primary End Point: The CONFIRM Study Trial Design

IF 1.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Open Access Journal of Clinical Trials Pub Date : 2019-11-01 DOI:10.2147/oajct.s224974
K. Jamil, S. Pappas, F. Wong, A. Sanyal
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引用次数: 1

Abstract

Background: Hepatorenal syndrome type 1 (HRS-1) is an uncommon, rapidly progressing, potentially fatal renal failure if left untreated. Terlipressin is a vasopressin analog that is fi rst-line therapy in combination with albumin for treatment of HRS-1 in countries outside of North America. In two previous Phase III clinical trials, terlipressin showed favorable effects on improvement in renal function compared with placebo; however, neither study showed a signi fi cant between-group difference in the primary end point. CONFIRM (NCT02770716) is an ongoing clinical trial designed to address operational challenges observed in the previous studies by using a novel, more clinically relevant primary end point than the previous studies. Methods: This Phase III, randomized, double-blind, multicenter study is expected to enroll about 300 patients at approximately 70 sites in the US and Canada. Patients with cirrhosis and ascites demonstrating renal impairment via rapidly progressive worsening of serum creatinine (SCr) level ( ≥ 199 μ mol/L [ ≥ 2.25 mg/dL] with a trajectory of SCr doubling over 2 weeks) are randomized 2:1 to receive either terlipressin 1 mg every 6 hrs as an IV bolus injection or placebo. The design of the study is generally similar to previous terlipressin prospective studies in the setting of HRS-1. A key feature differentiating this study from the previous ones centers around a novel, multi-component ef fi cacy variable that extends beyond the traditional outcome of improvement in renal function to include durability of treatment-related effects on renal replacement therapy (RRT) requirements and survival. To meet criteria for the primary ef fi cacy end point in CONFIRM, patients must show not only HRS reversal con fi rmed by two SCr values ≤ 1.5 mg/dL, but also survive, without RRT, for at least 10 days after achieving it. Conclusion: Data from this pivotal study will demonstrate whether terlipressin treatment is effective as measured by a new, clinically meaningful, multi-component primary ef fi cacy end point.
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证实肝肾综合征逆转是一个强大的多成分主要终点:确认研究试验设计
背景:1型肝肾综合征(HRS-1)是一种罕见的、进展迅速的、如果不及时治疗可能致命的肾衰竭。特利加压素是一种血管加压素类似物,在北美以外的国家,它是与白蛋白联合治疗HRS-1的一线疗法。在之前的两项III期临床试验中,与安慰剂相比,特利加压素在改善肾功能方面表现出良好的效果;然而,两项研究均未显示主要终点的组间差异显著。CONFIRM(NCT02770716)是一项正在进行的临床试验,旨在通过使用一种比先前研究更具临床相关性的新的主要终点来解决先前研究中观察到的操作挑战。方法:这项III期、随机、双盲、多中心研究预计将在美国和加拿大约70个地点招募约300名患者。肝硬化和腹水患者通过血清肌酐(SCr)水平迅速恶化(≥199μmol/L[≥2.25 mg/dL],SCr在2周内翻倍)而表现出肾功能损害,患者被2:1随机分组,每6小时接受1 mg特利加压素静脉推注或安慰剂。该研究的设计通常类似于之前在HRS-1环境中进行的特利加压素前瞻性研究。这项研究与之前的研究不同的一个关键特征是围绕一个新的、多组分的疗效变量,该变量超出了肾功能改善的传统结果,包括对肾脏替代治疗(RRT)需求和生存率的治疗相关影响的持久性。为了满足CONFIRM中主要疗效终点的标准,患者不仅必须表现出两个SCr值≤1.5 mg/dL所证实的HRS逆转,而且必须在没有RRT的情况下存活至少10天。结论:这项关键研究的数据将证明特利加压素治疗是否有效,多组分主要功效终点。
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来源期刊
Open Access Journal of Clinical Trials
Open Access Journal of Clinical Trials MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.90
自引率
0.00%
发文量
2
审稿时长
16 weeks
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