In a multicenter RCT of 204 high-risk hospitalized adults with moderate to severe COVID-19, oral Sabizabulin significantly reduced 60-day all-cause mortality compared to placebo (20.2% vs. 45.1%; OR 3.23, 95% CI 1.45–7.22, P = 0.0042; NNT = 4). Sabizabulin also reduced ICU days (43%), ventilator days (49%), and hospital days (26%). Benefits were consistent across subgroups. Sabizabulin demonstrates strong efficacy and safety in preventing COVID-19 progression to ARDS and death.

In a multicenter trial of 841 patients with severe COVID-19 and hypoxemic respiratory failure, high-dose dexamethasone did not reduce 60-day mortality compared to standard-dose dexamethasone (HR 0.96, 95% CI 0.69–1.33, P = 0.79). Among 333 non-intubated patients, respiratory support strategies (O₂ therapy, CPAP, or HFNO₂) showed no significant difference in 28-day invasive mechanical ventilation rates or 60-day mortality. Standard dexamethasone and patient-preferred oxygen strategies remain recommended.

In a multicenter RCT of 872 septic ICU patients on vasopressors, intravenous vitamin C increased the risk of death or persistent organ dysfunction at 28 days compared to placebo (44.5% vs. 38.5%; RR 1.21, 95% CI 1.04–1.40, P = 0.01). Mortality (35.4% vs. 31.6%) and organ dysfunction rates were higher but not statistically significant. No safety concerns were noted. These findings do not support the use of intravenous vitamin C in sepsis management.

In a multicenter RCT of 1554 patients with septic shock, a restrictive fluid strategy did not reduce 90-day mortality compared to standard fluid therapy (42.3% vs. 42.1%; adjusted difference 0.1 percentage points, 95% CI -4.7 to 4.9; P = 0.96). Serious adverse events and secondary outcomes were similar. These findings support continued use of standard fluid strategies per the Surviving Sepsis Campaign guidelines until further evidence warrants guideline modification.

In a multicenter RCT of 1065 ICU patients undergoing endotracheal intubation, a 500-mL fluid bolus did not significantly reduce vascular collapse compared to no fluid bolus (21.0% vs. 18.2%; absolute difference 2.8%, 95% CI -2.2% to 7.7%; P = 0.25). Secondary outcomes, including 28-day mortality (40.5% vs. 42.3%), were also similar. These findings suggest routine fluid bolus administration does not prevent vascular collapse during intubation.

In a meta-analysis of 2800 patients from the TTM and TTM2 trials, hypothermia at 33°C did not reduce 6-month all-cause mortality compared to normothermia (49.4% vs. 47.9%; RR 1.03, 95% CI 0.96–1.11, P = 0.41) or improve neurological outcomes (54.3% vs. 54.0%; RR 1.01, 95% CI 0.94–1.08, P = 0.88). No subgroup showed benefit with hypothermia. Evidence supports device-controlled normothermia (36–37.8°C) after out-of-hospital cardiac arrest.

In a multicenter RCT of 150 COVID-19 patients requiring mechanical ventilation, early tracheostomy (≤7 days) did not significantly reduce total ventilator days compared to late tracheostomy (≥10 days) in the ITT analysis (19.6 vs. 21.1 days; P = 0.5). PP analysis showed fewer ventilator days with early tracheostomy (22.3 vs. 30.3 days; P = 0.0064). Mortality and ICU length of stay were similar. While underpowered, early tracheostomy may be considered for select patients needing prolonged ventilation.

In a multicenter RCT of 362 patients with COVID-19 pneumonia and mild hypoxemia, high-flow nasal oxygen (HFNO) did not significantly reduce the escalation of respiratory support compared to conventional oxygen therapy (30.3% vs. 38.6%; P = 0.09). Secondary outcomes, including clinical recovery and ICU admission, were similar. The study was underpowered, so a potential clinically meaningful benefit of HFNO cannot be definitively excluded.

In a multicenter RCT of 400 patients with COVID-19 and hypoxemic respiratory failure, awake prone positioning did not significantly reduce 30-day intubation rates compared to usual care (34.1% vs. 40.5%; P = 0.20). Secondary outcomes, including 60-day mortality and ventilator-free days, were also similar. While the study did not achieve its target prone duration, a clinically meaningful benefit cannot be excluded. Awake prone positioning remains a reasonable intervention for pre-intubation hypoxemic respiratory failure.

In a multicenter RCT of 382 mechanically ventilated patients with severe stroke, early tracheostomy (≤5 days) did not significantly improve 6-month functional outcomes without severe disability (mRS ≤4) compared to standard tracheostomy (43.5% vs. 47.1%; OR 0.93, 95% CI 0.60–1.42; P = 0.73). Serious adverse events were similar between groups. Findings suggest no clear benefit of early tracheostomy, though a smaller effect cannot be excluded due to wide confidence intervals.

In a multicenter trial of 553 critically ill children requiring non-invasive respiratory support post-extubation, HFNC (50.5 hrs) failed to demonstrate non-inferiority to CPAP (42.9 hrs) for time to liberation from respiratory support (adjusted HR 0.83; 1-sided 97.5% CI, 0.70–∞). Secondary 180-day mortality was higher with HFNC (5.6% vs. 2.4%). Findings suggest CPAP may be preferred for post-extubation respiratory support in young childre

In a phase II trial of esmolol for septic shock, no significant differences were found in norepinephrine-equivalent dose, time to shock reversal, or inflammatory markers (except lower CRP in the esmolol group). Reduced oxygen consumption was noted in a subset of esmolol patients. While prior studies suggested improved hemodynamics and mortality benefits, this trial highlights the need for a large, well-powered RCT to evaluate patient-centered outcomes of esmolol in septic shock.