To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79–1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66–1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75–1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. ClinicalTrials.gov number: NCT04001504 Summary of the Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) main findings. Among patients hospitalized for ACS, in-hospital double-dose influenza vaccination did not reduce the rates of major cardiovascular and pulmonary events at 12 months as compared with standard-dose vaccination 30 days after randomization. (Left panel) Summary of the design and primary outcome of the VIP-ACS trial. (Right upper figure) The primary outcome was a hierarchical composite analysed by unmatched win ratio method. (Right lower figure) The primary outcome was a time-to-event analysis with the use of unadjusted Cox proportional hazards models.

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The 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. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally 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 (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO₂ of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Introduction The V-GOOD study evaluated the effectiveness of trimetazidine modified-release (MR) 80 mg once daily (OD) in patients with chronic coronary syndrome (CCS) who remained symptomatic despite antianginal therapies in routine clinical practice. Methods This prospective, observational study involved 1026 adult outpatients with symptomatic CCS from 70 sites in Brazil who were prescribed trimetazidine MR 80 mg OD plus background antianginal treatment. Data on number of angina attacks, short-acting nitrate consumption, prevalence of angina-free patients, severity of angina, patient-reported daily physical activity impairment, treatment adherence, tolerability, and cardiologist and patient satisfaction were collected at baseline (V1), then at 1 month (V2) and 3 months (V3). Results Following the addition of trimetazidine MR 80 mg OD, the mean ± standard deviation number of angina attacks per week decreased from 3.1 ± 2.8 at V1 to 1.0 ± 2.1 at V2, and 0.7 ± 1.7 at V3, with concurrent reductions in short-acting nitrate consumption, patient-reported daily physical activity impairment and the proportion of patients with limiting angina (Canadian Cardiovascular Society class III or IV), and increases in the proportion of angina-free patients (all p < 0.001 vs. V1). Most cardiologists rated trimetazidine MR 80 mg OD as satisfactory/very satisfactory (90.7% for effectiveness and 94.8% for tolerability); most patients rated the treatment schedule as convenient/very convenient (97.2%) and satisfactory/very satisfactory (97.1%). Treatment was well tolerated. Conclusions These data support the symptomatic benefits and good tolerability associated with adding trimetazidine MR 80 mg OD to other antianginal therapies in patients with persistent symptoms. Graphical abstract available for this article. Trial registration number NCT06464276. Graphical Abstract

Background: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. Objective: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. Methods: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. Outcomes: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. Conclusion: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.