趋化因子受体 2（CCR2）拮抗剂 DMX-200 联合坎地沙坦治疗 COVID-19：一项随机对照试验。

Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial.

机构信息

NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia

Department of Renal Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia.

出版信息

BMJ Open. 2024 Oct 22;14(10):e081790. doi: 10.1136/bmjopen-2023-081790.

DOI:10.1136/bmjopen-2023-081790

PMID:39438096

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11499840/

Abstract

OBJECTIVE

To determine whether a chemokine receptor type 2 antagonist, DMX-200 (repagermanium), in combination with an angiotensin receptor blocker, candesartan, improves clinical outcomes in people with COVID-19.

DESIGN

Prospective, multicentre, double-blind, placebo-controlled trial.

SETTING

Ten acute care hospitals in India.

PARTICIPANTS

Adults <65 years old intended for hospital admission with moderate/severe COVID-19 disease (respiratory rate ≥24 breaths per minute or oxygen saturation ≤93% on room air).

INTERVENTION

DMX-200 120 mg two times per day, or placebo, on background of titratable candesartan commencing at 4 mg two times per day, for 28 days.

MAIN OUTCOME MEASURES

The primary endpoint was COVID-19 disease severity on a modified WHO Clinical Progression Scale (WHO scale) on day 14. Secondary outcomes included the WHO scale at days 28, 60, 90 and 180; intensive care unit (ICU) admission, respiratory failure or death within 28 days; length of hospitalisation; and requirement for ventilatory support or dialysis.

RESULTS

Between December 2021 and August 2022, 518 people were screened, with 49 randomised to DMX-200 or placebo on a background of candesartan. The study was terminated early due to recruitment barriers, including an external requirement to restrict enrolment to adults <65 years old, contributing to a 91% screen failure rate. The median WHO Clinical Progression Scale (WHO scale) score at day 14 for both groups was 1 (IQR 1-1), indicating most participants were discharged with no limitations on activities by this time. Formal comparison was not performed due to the small sample size. One participant receiving DMX-200 died of COVID-19 disease progression. No participants required ICU admission, ventilation or dialysis. Median length of hospitalisation in both groups was 6 days (IQR 6-7 days). WHO scale scores were similar at 28, 60, 90 and 180 days.

CONCLUSION

Due to recruitment barriers, the study was unable to determine whether DMX-200 improves clinical outcomes in people with COVID-19.

TRIAL REGISTRATION NUMBER

ClinicalTrials.gov NCT05122182.

摘要

目的

确定趋化因子受体 2 拮抗剂 DMX-200（雷帕霉素）与血管紧张素受体阻滞剂坎地沙坦联合使用是否能改善 COVID-19 患者的临床结局。

设计

前瞻性、多中心、双盲、安慰剂对照试验。

地点

印度的 10 家急性护理医院。

参与者

年龄<65 岁、拟住院治疗的中度/重度 COVID-19 患者（呼吸频率≥24 次/分钟或在室内空气下血氧饱和度≤93%）。

干预措施

DMX-200 120mg，每日两次，或安慰剂，同时使用可滴定坎地沙坦，起始剂量为 4mg，每日两次，治疗 28 天。

主要观察指标

主要终点是第 14 天改良的世界卫生组织临床进展量表（WHO 量表）上的 COVID-19 疾病严重程度。次要结局包括第 28、60、90 和 180 天的 WHO 量表；28 天内 ICU 入院、呼吸衰竭或死亡；住院时间；以及需要通气支持或透析的情况。

结果

2021 年 12 月至 2022 年 8 月，共筛选了 518 人，其中 49 人随机分配至 DMX-200 或安慰剂加用坎地沙坦。由于招募障碍，包括外部要求将入组年龄限制在<65 岁以下，导致 91%的筛选失败，研究提前终止。两组第 14 天的中位 WHO 临床进展量表（WHO 量表）评分均为 1（IQR 1-1），表明大多数患者此时已出院，活动不受限制。由于样本量小，未进行正式比较。一名接受 DMX-200 治疗的患者死于 COVID-19 疾病进展。没有患者需要 ICU 入院、通气或透析。两组的中位住院时间均为 6 天（IQR 6-7 天）。两组在第 28、60、90 和 180 天的 WHO 量表评分相似。