ABSTRACT
Rationale There are few treatment options for severe COVID-19 pneumonia. Opaganib is an oral treatment under investigation. Objective Evaluate opaganib treatment in hospitalized patients with severe COVID-19 pneumonia. Methods A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 60 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n=230; 500mg twice daily) or matching placebo (n=233) for 14 days. Main Outcome Measurements Primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28- and 42-days. Main Results Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FiO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FiO2 levels at or below the median value ([≤]60%) had better outcomes after opaganib treatment (n=117) compared to placebo (n=134). The proportion of patients with [≤]60% FIO2 at baseline that no longer required supplemental oxygen (at least 24 hours) by day 14 of opaganib treatment increased (76.9% vs 63.4%: p-value =0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs 17.91%; p-value=0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs 16.7%; p-value=0.019) by day 42. No new safety concerns observed. Conclusions Post-hoc analysis supports opaganib benefit in COVID-19 severe pneumonia patients that require lower supplemental oxygen ([≤]60% FiO2). Further studies are warranted.
Subject(s)
COVID-19 , Pneumonia , Severe Acute Respiratory SyndromeABSTRACT
Background: Coronavirus Disease 2019 (Covid-19) pandemic since its first confirmed case, has changed the world. The need for accurate and truthful information is vital. Mexico and Latin America have been widely affected, so having local epidemiological data, will be of great clinical utility. Methods: A total of 33 hospitalized patients with Covid-19 pneumonia (either severe or critical) were identified from electronic health record in a third level care private hospital in Mexico City from March 13rd to April 13rd, 2020. We conducted a descriptive study of patients for characterization of the clinical, laboratory and radiologic findings, as well as complications. Results: The mean age was 60.6 (12.68) years and 23 (69.7%) were males. Twenty-three patients (69.6%) were overweight or obese. The median duration of symptoms before admission was 7 days. All the patients required mechanical invasive ventilation. The median duration of the mechanical ventilation was 12(2.6) days and all patients were extubated except one. All patients were started on antiviral treatment in the first 24 hours after admission once the diagnosis of Covid19 pneumonia was made. There was no difference between the treatment option and the length of stay. The extubation rate was higher (91.6%) than in other series, with no fatalities even though they were treated with different regimens. Conclusions: This one-centre experience describes the epidemiology, treatment and outcome of 33 patients with severe or critical COVID pneumonia admitted to the ICU. Most patients in our series were overweight or obese male, which we observed were of higher risk to present critical pneumonia, as well as high levels of Interleukin-6. The foregoing is relevant, due to the high incidence of these comorbidities in our country.