Henry Ford Hospital System, Detroit, MI, USA.
Regions Hospital, Health Partners, St. Paul, MN, USA.
Crit Care. 2020 Aug 14;24(1):502. doi: 10.1186/s13054-020-03220-x.
Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia.
A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study.
In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥ 1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died during the 30 days after randomization. Among patients with severe COVID-19 pneumonia, the median time to recovery with Auxora was 5 days versus 12 days with SOC; the recovery rate ratio was 1.87 (95% CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction = 32%; 95% CI, - 0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO/FiO = 101-200.
Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from the early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study.
ClinicalTrials.gov, NCT04345614 . Submitted on 7 April 2020.
钙释放激活钙 (CRAC) 通道抑制剂可稳定肺内皮细胞并阻断促炎细胞因子的释放，从而减轻 COVID-19 患者观察到的呼吸并发症。本研究旨在研究 Auxora（一种新型静脉给予的 CRAC 通道抑制剂）在患有严重或危重症 COVID-19 肺炎的成年人中的安全性和疗效。
对患有严重或危重症 COVID-19 肺炎的成年人进行了一项 Auxora 的随机、对照、开放性研究。患者以 2:1 的比例随机分为接受每日一次 Auxora 治疗的三组与单独接受标准护理 (SOC) 的一组。主要目的是评估 Auxora 的安全性和耐受性。根据 FDA 指南，为允许过渡到随机、盲法、安慰剂对照研究，提前停止了研究入组。
共有 17 例患有严重 COVID-19 肺炎和 3 例患有危重症 COVID-19 肺炎的患者被随机分配至 Auxora 组，9 例患有严重 COVID-19 肺炎和 1 例患有危重症 COVID-19 肺炎的患者被随机分配至 SOC 组。接受 Auxora 和 SOC 的患者发生≥1 例不良事件的比例相似（分别为 75%和 80%）。接受 Auxora 的患者发生严重不良事件的比例低于 SOC（分别为 30%和 50%）。在随机分组后 30 天内，2 名（10%）接受 Auxora 治疗的患者和 2 名（20%）接受 SOC 治疗的患者死亡。在患有严重 COVID-19 肺炎的患者中，与 SOC 相比，Auxora 组的中位恢复时间为 5 天，SOC 组为 12 天；恢复率比为 1.87（95%CI，0.72，4.89）。接受 Auxora 的严重 COVID-19 肺炎患者中有 18%需要进行有创机械通气，而接受 SOC 的患者有 50%需要进行有创机械通气（绝对风险降低=32%；95%CI，-0.07，0.71）。接受 Auxora 的患者的 8 分等级量表测量的结局明显改善，基线 PaO/FiO2=101-200 的患者尤其如此。
Auxora 在患有严重或危重症 COVID-19 肺炎的患者中表现出良好的安全性，并改善了严重 COVID-19 肺炎患者的结局。然而，这些结果受到开放性研究设计和监管指导下提前停止入组导致的患者数量少的限制。Auxora 在严重 COVID-19 肺炎患者中对呼吸并发症的影响将在计划的随机、盲法、安慰剂对照研究中进一步评估。
ClinicalTrials.gov，NCT04345614。于 2020 年 4 月 7 日提交。
