Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial

Abstract

Background: 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. Methods: 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. Results: 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 8point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO 2 /FiO 2 = 101-200.

Evaluating the methodology of studies conducted during the global COVID-19 pandemic: A systematic review of randomized controlled trials

“…A previous study reported that there were proportionally fewer well-designed RCTs published during an urgent situation. Chang et al [36] found that among 338 COVID-19 registered trials, only 16 had adopted randomized, single-blind or double-blind designs, and only 8 studies had used randomized, double-blind, placebo-controlled design. Xie et al [37] also found that RCT was the most common design in 51 pilot studies, but only 10 of those studies had used blinding.…”

Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of in vitro, in vivo, and clinical trials

“…In an RCT on severe or critical COVID-19, the proportion of patients who received invasive MV or died was lower in the Auxora-treated group than the control group (3 out of 17 [18%] vs. 5 out of 9 [6%]; HR 0.23, 95% CI 0.05 to 0.96; P < 0.05) and the mean difference in the 8-point ordinal scale was statistically significant on day 6 and day 9 to 12 ( P < 0.05) 79 ( Table 3 ).…”

“…It has been suggested that Auxora may protect against pulmonary endothelial damage and cytokine storm 119 , 120 . This agent has been shown to be effective in terms of survival and clinical improvement in one small-scale RCT for severe or critical COVID-19 79 .…”

A Systematic Review and Network Meta-Analysis for COVID-19 Treatments

“…A total of 74 studies 2, 5, 15-18, 36-39, 41-44, 47-54, 56, 57, 59-63, 65-67, 69, 70, 72, 74-76, 78, 79, 82, 83, 85, 87, 88, 90-92, 94-97, 99, 100, 103-121, 125 including 48622 patients reported all-cause mortality. After filtering out treatments with small sample size following the specified criteria, the network included azithromycin, hydroxychloroquine, hydroxychloroquine plus azithromycin, colchicine, arbidol (umifenovir), favipiravir, remdesivir, lopinavir/ritonavir, convalescent plasma, methylprednisolone, dexamethasone, hydrocortisone, immunoglobulin, interferon beta, recombinant human granulocyte colony-stimulating factor (GCSF), tocilizumab, vitamin D 3 , baricitinib plus remdesivir, sulodexide and SOC.…”