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Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial.
Bruen, Charles; Al-Saadi, Mukhtar; Michelson, Edward A; Tanios, Maged; Mendoza-Ayala, Raul; Miller, Joseph; Zhang, Jeffrey; Stauderman, Kenneth; Hebbar, Sudarshan; Hou, Peter C.
  • 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.
Crit Care ; 26(1): 101, 2022 04 08.
Article in English | MEDLINE | ID: covidwho-1779665
ABSTRACT

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 PaO2/FiO2 ratio > 75 and ≤ 300. The PaO2/FiO2 was imputed from a SpO2/FiO2 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 PaO2/FiO2≤ 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 PaO2/FiO2 ≤ 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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pyrazines / Respiratory Distress Syndrome / Benzamides / Calcium Release Activated Calcium Channels / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Adult / Humans Language: English Journal: Crit Care Year: 2022 Document Type: Article Affiliation country: S13054-022-03964-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pyrazines / Respiratory Distress Syndrome / Benzamides / Calcium Release Activated Calcium Channels / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Adult / Humans Language: English Journal: Crit Care Year: 2022 Document Type: Article Affiliation country: S13054-022-03964-8