Hexasodium fytate for the treatment of calciphylaxis: a randomised, double-blind, phase 3, placebo-controlled trial with an open-label extension.

IF 9.6 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

EClinicalMedicine Pub Date : 2024-08-16 eCollection Date: 2024-09-01 DOI:10.1016/j.eclinm.2024.102784

Smeeta Sinha, Sagar U Nigwekar, Vincent Brandenburg, Lisa J Gould, Thomas E Serena, Sharon M Moe, George R Aronoff, Dinesh K Chatoth, Jeffrey L Hymes, Kevin J Carroll, Gabriela Alperovich, Laurence H Keller, Joan Perelló, Alex Gold, Glenn M Chertow

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引用次数: 0

Abstract

Background: In the CALCIPHYX trial, we investigated hexasodium fytate, an inhibitor of vascular calcification, for the treatment of calcific uraemic arteriolopathy (calciphylaxis), a rare condition characterised by painful, non-healing skin lesions.

Methods: In this international, phase 3, randomised, double-blind, placebo-controlled trial, adults with an ulcerated calciphylaxis lesion and pain visual analogue scale (VAS) score ≥50/100 were randomised 1:1 to hexasodium fytate 7 mg/kg or placebo intravenously during maintenance haemodialysis. Primary efficacy outcomes were an 8-item modification of the Bates-Jensen Wound Assessment Tool (BWAT-CUA) and Pain VAS in the intention-to-treat population. ClinicalTrials.gov number: NCT04195906.

Findings: Overall, 34/37 patients randomised to hexasodium fytate and 26/34 patients randomised to placebo completed the 12-week randomised treatment period. At Week 12, both groups (hexasodium fytate versus placebo) showed similar improvements in BWAT-CUA (mean [standard deviation (SD)], -5.3 [5.2] versus -6.0 [6.2]; least squares mean difference, 0.3 [96% confidence interval (CI): -2.5, 3.0]; p = 0.88) and Pain VAS (mean [SD], -19.5 [26.9] versus -32.2 [38.5]; least squares mean difference, 11.5 [96% CI: -4.8, 27.8]; p = 0.15). One patient randomised to placebo briefly received hexasodium fytate in error. Serious adverse events through Week 12 included: calciphylaxis-related events leading to hospitalisation (2/38 [5%] versus 11/33 [33%]) and death (1/38 [3%] versus 5/33 [15%]). During the subsequent 12 weeks of open-label hexasodium fytate and 4 weeks of follow-up, there were no additional calciphylaxis-related events leading to hospitalisation. Over the course of the entire trial, deaths were 2/38 [5%] for the hexasodium fytate group and 7/33 [21%] for the placebo group.

Interpretation: In patients with calciphylaxis, BWAT-CUA and Pain VAS improved similarly in hexasodium fytate- and placebo-treated patients; over the course of the entire trial, there were fewer deaths and calciphylaxis-related events leading to hospitalisation in the hexasodium fytate group.

Funding: Funded by Sanifit, a CSL Vifor company.

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治疗钙血症的非他酸六钠：一项随机、双盲、第 3 期、安慰剂对照试验，以及一项开放标签扩展试验。

研究背景在 CALCIPHYX 试验中，我们研究了抑制血管钙化的非他酸己钠治疗钙化性尿毒症动脉炎（钙化性动脉炎）的方法：在这项3期随机、双盲、安慰剂对照的国际性试验中，患有钙化性动脉炎溃疡且疼痛视觉模拟量表（VAS）评分≥50/100的成人按1:1的比例在维持性血液透析期间被随机分配到静脉注射7 mg/kg的非他酸己钠或安慰剂中。在意向治疗人群中，主要疗效结果是贝茨-詹森伤口评估工具（BWAT-CUA）的8项修订版和疼痛VAS。ClinicalTrials.gov 编号：NCT04195906.Findings:总体而言，34/37 名随机接受非替酸己钠治疗的患者和 26/34 名随机接受安慰剂治疗的患者完成了为期 12 周的随机治疗。第12周时，两组患者（非他酸己钠与安慰剂）的BWAT-CUA改善情况相似（平均值[标准差（SD）]，-5.3 [5.2] 对 -6.0 [6.2]；最小二乘法平均差，0.3 [96% 置信区间 (CI)：-2.5，3.0]；p = 0.88）和疼痛 VAS（平均值 [标准差 (SD)：-19.5 [26.9] 对 -32.2 [38.5]；最小二乘平均差：11.5 [96% CI：-4.8，27.8]；p = 0.15）。一名随机接受安慰剂治疗的患者错误地短暂接受了己烯雌酚钠治疗。第12周发生的严重不良事件包括：导致住院的钙虹膜炎相关事件（2/38[5%]对11/33[33%]）和死亡（1/38[3%]对5/33[15%]）。在随后12周的开放标签己钠盐治疗和4周的随访期间，没有再发生导致住院的钙虹膜炎相关事件。在整个试验过程中，非他酸己钠组的死亡人数为2/38[5%]，安慰剂组为7/33[21%]：在钙虹膜炎患者中，己二酸六钠治疗组和安慰剂治疗组的BWAT-CUA和疼痛VAS改善程度相似；在整个试验过程中，己二酸六钠治疗组的死亡人数和导致住院的钙虹膜炎相关事件较少：由 CSL Vifor 旗下公司 Sanifit 资助。

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来源期刊

EClinicalMedicine Medicine-Medicine (all)

CiteScore

18.90

自引率

1.30%

发文量

506

审稿时长

22 days

期刊介绍： eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.