Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial.

Autor: Bruen C; Regions Hospital, Health Partners, St. Paul, MN, USA., Al-Saadi M; Houston Methodist Hospital, Houston, TX, USA., Michelson EA; Department of Emergency Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA., Tanios M; MemorialCare Long Beach Medical Center, Long Beach, CA, USA., Mendoza-Ayala R; Aurora BayCare Medical Center, Green Bay, WI, USA., Miller J; Henry Ford Hospital System, Detroit, MI, USA., Zhang J; Princeton Pharmatech, Princeton, NJ, USA., Stauderman K; CalciMedica, Inc, 505 Coast Blvd. South Suite 307, La Jolla, CA, 92037, USA., Hebbar S; CalciMedica, Inc, 505 Coast Blvd. South Suite 307, La Jolla, CA, 92037, USA. sudarshan@calcimedica.com., Hou PC; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Critical care (London, England) [Crit Care] 2022 Apr 08; Vol. 26 (1), pp. 101. Date of Electronic Publication: 2022 Apr 08.
DOI: 10.1186/s13054-022-03964-8
Abstrakt: Background: Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia.
Methods: CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. Eligible patients were adults with ≥ 1 symptom consistent with COVID-19 infection, a diagnosis of COVID-19 confirmed by laboratory testing using polymerase chain reaction or other assay, and pneumonia documented by chest imaging. Patients were also required to be receiving oxygen therapy using either a high flow or low flow nasal cannula at the time of enrolment and have at the time of enrollment a baseline imputed PaO 2 /FiO 2 ratio > 75 and ≤ 300. The PaO 2 /FiO 2 was imputed from a SpO 2 /FiO 2 determine by pulse oximetry using a non-linear equation. Patients could not be receiving either non-invasive or invasive mechanical ventilation at the time of enrolment. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and utilization of standard of care medications prohibited by regulatory guidance, the trial was stopped early.
Results: The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO 2 /FiO 2 ≤ 200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P = 0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P = 0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P = 0.0165). Similar trends were noted in all randomized patients, patients on high flow nasal cannula at baseline or those with a baseline imputed PaO 2 /FiO 2  ≤ 100. Serious adverse events (SAEs) were less frequent in patients treated with Auxora vs. placebo and occurred in 34 patients (24.1%) receiving Auxora and 49 (35.0%) receiving placebo (P = 0.0616). The most common SAEs were respiratory failure, acute respiratory distress syndrome, and pneumonia.
Conclusions: Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in patients with severe COVID-19 pneumonia are warranted. Trial registration NCT04345614.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: