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

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..

Medienart:	E-Artikel

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	Zur Gesamtaufnahme - volume:26
Enthalten in:	Critical care - 26(2022), 1 vom: 08. Apr.

Sprache:	Englisch

Beteiligte Personen:	Bruen, Charles [VerfasserIn] Al-Saadi, Mukhtar [VerfasserIn] Michelson, Edward A. [VerfasserIn] Tanios, Maged [VerfasserIn] Mendoza-Ayala, Raul [VerfasserIn] Miller, Joseph [VerfasserIn] Zhang, Jeffrey [VerfasserIn] Stauderman, Kenneth [VerfasserIn] Hebbar, Sudarshan [VerfasserIn] Hou, Peter C. [VerfasserIn]

Links:	Volltext [kostenfrei]

BKL:	44.00 / Medizin: Allgemeines / Medizin: Allgemeines

Anmerkungen:	© The Author(s) 2022

doi:	10.1186/s13054-022-03964-8

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC2130091296