ABSTRACT
Background. EXO-CD24 is a novel inhaled drug of exosomes displaying CD24, a protein with anti-inflammatory properties. We evaluated the safety and potential efficacy of EXO-CD24, in a phase II, randomized, single-blinded clinical trial of EXO-CD24 in hospitalized patients with moderate or severe COVID-19, following the preliminary safety and efficacy results of a phase 1 study (ClinicalTrials.gov: NCT04747574). Methods. Two tertiary care hospitals in Athens, Greece participated. Patients received either 109 or 1010 exosome particles per dose, once per day for 5 days and were followed for 28 days. Safety and efficacy measures (including respiratory rate < 23 b/ min and pulse oximetry SpO2>= 94% on room air, oxygen need and levels of inflammatory biomarkers i.e. CRP, LDH, ferritin, fibrinogen and d-dimers) were compared between groups at days 3, 5 and 7. A separate analysis was conducted comparing the clinical course of treated patients with that of a control cohort (n=70 patients) matched by propensity scoring out of a similar period hospitalized cohort (n=202) that did not participate in the study. Results. Between June 9th and August 3rd 2021, 91 patients underwent randomization: 45 in group A and 46 in group B (109 vs. 1010 exosome particles per dose). Mean age was 49.4 (+/- 13.2) years and 74.4% were male. Mean time from symptom onset to randomization was 8 days. Improvement in respiratory rate and pulse oximetry was noted in 72 out of 86 (83.7%) and 55 out of 86 (64%) analyzed patients. Day 7 inflammatory indices levels dropped at least 50% from baseline admission values in 72 out of 86 (82.8%) analyzed patients (p< 0.001). No treatment-related adverse events were reported. Comparison with the propensity score matched group showed statistically significant differences in the same parameters (p<= 0.01 for all comparisons). Conclusion. Our results suggest safety and potential efficacy of EXO-CD24 on clinical and laboratory parameters of moderate or severe COVID-19, that deserve further investigation in a phase 3 study. (Funded by Athens Medical Society. ClinicalTrials.gov: NCT04902183, EU Clinical Trials Register EudraCT Number 2021-002184-22).
ABSTRACT
Background. There are few real-world data on the use of remdesivir (RDV) looking at timing of initiation in relation to symptom onset and severity of presenting disease. Methods. We conducted multi-country retrospective study of clinical practice and use of RDV in COVID-19 patients. De-identified medical records data were entered into an e-CRF. Primary endpoints were all-cause mortality at day 28 and hospitalization duration. We assessed time from symptom onset to RDV start and re-admission. We included adults with PCR-confirmed symptomatic COVID-19 who were hospitalized after Aug 31, 2020 and received at least 1 dose of RDV. Descriptive analyses were conducted. Kaplan-Meier methods were used to calculate the mortality rate, LogRank test to compare groups defined by severity of disease. Competing risk regression with discharge and death as competing events was used to estimate duration of hospitalization, and Gray's test to compare the groups. Results. 448 patients in 5 countries (12 sites) were included. Demographics are summarized (table) by 3 disease severity groups at baseline: no supplemental oxygen (NSO), low flow oxygen ≤6 L/min (LFO), and high-flow oxygen > 6L/min (HFO). No demographic differences were found between groups except for the higher percentage of cancer/chemotherapy patients in NSO group. Corticosteroids use was HFO 73.6%, LFO 62.7%, NSO 58.0%. Mortality rate was significantly lower in NSO, and LFO groups compared with HFO (6.2%, 10.2%, 23.6%, respectively;Fig1). Median duration of hospitalization was 9 (95%CI 8-10), 9 (8-9), 13 (10-15) days, respectively (Fig2). Median time from first symptom to RDV start was 7 days in all 3 groups. Patients started RDV on day 1 of hospitalization in HFO and LFO and day 2 on NSO groups. And received a 5 day course (median). Readmission within 28-days of discharge was < 5% and similar across all 3 groups. Conclusion. In this real-world cohort of COVID-19 positive hospitalized patients, RDV use was consistent across countries. RDV was started within a median of 7 days from symptom within 2 days of admission and given for a median of 5 days. Higher mortality rate and duration of hospitalization was seen in the HFO group and similar rates seen in the LFO and NSO groups. Readmission was consistently low across all 3 groups.