Photo Credit: Jesus Rodriguez

The following is a summary of “Alteplase in COVID-19 severe hypoxemic respiratory failure: the TRISTARDS multicenter randomized trial,” published in the November 2024 issue of Critical Care by Landoni et al. 

Pulmonary intravascular thrombus formation is commonly observed in respiratory failure, including SARS-CoV-2 infection (COVID-19) cases.  

Researchers conducted a retrospective study to examine the efficacy and safety of alteplase thrombolysis in severe hypoxemic respiratory failure due to COVID-19.  

They randomized participants to receive alteplase (low- or high-dose) for 5 days along with the standard of care (SOC) or without SOC, the primary endpoint was the time to clinical improvement, defined as a ≥2-point decrease on the WHO Clinical Progression Scale or hospital discharge, analyzed up to Day 28 while, secondary endpoints included all-cause mortality at Day 28, with treatment failure and changes in arterial oxygen partial pressure to fractional inspired oxygen (PaO₂ /FiO₂) ratio on Day 6 compared to baseline.  

The results showed 69 patients were randomized to receive alteplase (low- or high-dose) and 35 to SOC, 65% of patients were on high-flow oxygen or non-invasive ventilation at baseline. The median time to clinical improvement was 25 days in the alteplase group and >28 days (median not reached) in the SOC group. All-cause mortality was 8/69 (12%) in the alteplase group vs 10/35 (29%) in the SOC group, respectively (unadjusted risk difference [RD], −17% [95% CI −34 to 0], P =0.047; adjusted RD, −16% [95% CI −31 to 1], P =0.058). The PaO₂ /FiO₂ ratio (mean [standard deviation]) rose by +30 (84) mmHg in the alteplase group and reduced by −12 (59) mmHg in the SOC group (adjusted mean difference vs. SOC, P =0.052). The differences were more significant in patients receiving high-dose alteplase and those not receiving invasive ventilation; 18 patients (26.1%) in the alteplase group discontinued treatment due to adverse events, while major bleeding was most recurring with alteplase than with SOC (9 vs 0 patients); no bleeding was fatal. The study closed early due to insufficient patient recruitment.  

Investigators concluded the alteplase did not accelerate clinical recovery in patients with COVID-19 and severe hypoxemic respiratory failure. While potential benefits in specific patient subgroups were observed.  

Source: annalsofintensivecare.springeropen.com/articles/10.1186/s13613-024-01386-z