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 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.

Initial clinical experience with the Quantra QStat System in adult trauma patients.

BACKGROUND: Whole blood viscoelastic testing (VET) devices are routinely used in a variety of clinical settings to assess hemostasis. The Quantra QStat System is a cartridge-based point of care VET device that measures changes in clot stiffness during coagulation and fibrinolysis using ultrasound detection of resonance. The objective of this study was to assess the ability of the Quantra QStat System to detect coagulopathies in trauma patients. METHODS: A multicenter observational study was conducted on adult subjects at two level 1 trauma centers. For each subject, whole blood samples were drawn upon arrival to the emergency department and again, in some cases, after administration of blood products and/or antifibrinolytics. Samples were analyzed on the Quantra in parallel to ROTEM delta. The QStat cartridge provides measures of Clot Time (CT), Clot Stiffness (CS), Fibrinogen and Platelet Contributions to clot stiffness (FCS and PCS), and Clot Stability to Lysis (CSL). Data analyses included linear regression of Quantra and ROTEM parameters and an assessment of the concordance of the two devices for the assessment of hyperfibrinolysis. RESULTS: A total of 56 patients were analyzed. 42% of samples had a low QStat CS value suggestive of an hypocoagulable state. The low stiffness values could be attributed to either low PCS, FCS or combination. Additionally, 13% of samples showed evidence of hyperfibrinolysis based on the QStat CSL parameter. Samples analyzed with ROTEM assays showed a lower prevalence of low CS and hyperfibrinolysis based on EXTEM and FIBTEM results. The correlation of CS, FCS and CT versus equivalent ROTEM parameters was strong with r-values of 0.83, 0.79 and 0.79, respectively. DISCUSSION: This first clinical experience with the Quantra in trauma patients showed that the QStat Cartridge was strongly correlated with ROTEM parameters and that it could detect coagulopathies associated with critical bleeding. LEVEL OF EVIDENCE: Diagnostic test, Level II.