1.
Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial.
Miller, J, Bruen, C, Schnaus, M, Zhang, J, Ali, S, Lind, A, Stoecker, Z, Stauderman, K, Hebbar, S
Critical care (London, England). 2020;(1):502
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 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2 = 101-200. CONCLUSIONS 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. TRIAL REGISTRATION ClinicalTrials.gov, NCT04345614 . Submitted on 7 April 2020.
2.
Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.
Cavalcanti, AB, Zampieri, FG, Rosa, RG, Azevedo, LCP, Veiga, VC, Avezum, A, Damiani, LP, Marcadenti, A, Kawano-Dourado, L, Lisboa, T, et al
The New England journal of medicine. 2020;(21):2041-2052
-
-
Free full text
-
Abstract
BACKGROUND Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).
3.
Wearing of Cloth or Disposable Surgical Face Masks has no Effect on Vigorous Exercise Performance in Healthy Individuals.
Shaw, K, Butcher, S, Ko, J, Zello, GA, Chilibeck, PD
International journal of environmental research and public health. 2020;(21)
Abstract
Wearing face masks is recommended for the prevention of contracting or exposing others to cardiorespiratory infections, such as COVID-19. Controversy exists on whether wearing face masks during vigorous exercise affects performance. We used a randomized, counterbalanced cross-over design to evaluate the effects of wearing a surgical mask, a cloth mask, or no mask in 14 participants (7 men and 7 women; 28.2 ± 8.7 y) during a cycle ergometry test to exhaustion. Arterial oxygen saturation (pulse oximetry) and tissue oxygenation index (indicator of hemoglobin saturation/desaturation) at vastus lateralis (near-infrared spectroscopy) were assessed throughout the exercise tests. Wearing face masks had no effect on performance (time to exhaustion (mean ± SD): no mask 622 ± 141 s, surgical mask 657 ± 158 s, cloth mask 637 ± 153 s (p = 0.20); peak power: no mask 234 ± 56 W, surgical mask 241 ± 57 W, cloth mask 241 ± 51 W (p = 0.49)). When expressed relative to peak exercise performance, no differences were evident between wearing or not wearing a mask for arterial oxygen saturation, tissue oxygenation index, rating of perceived exertion, or heart rate at any time during the exercise tests. Wearing a face mask during vigorous exercise had no discernable detrimental effect on blood or muscle oxygenation, and exercise performance in young, healthy participants (ClinicalTrials.gov, NCT04557605).