TRISTARDS
Trial question
What is the role of alteplase in patients with COVID-19-associated severe hypoxemic respiratory failure?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
31.0% female
69.0% male
N = 104
104 patients (32 female, 72 male).
Inclusion criteria: patients with COVID-19-associated severe hypoxemic respiratory failure.
Key exclusion criteria: PE with hemodynamic instability; an indication for therapeutic dosing of anticoagulants; invasive mechanical ventilation for > 48 hours; history of chronic pulmonary disease, primary pulmonary arterial hypertension, bleeding disorder, or ICH in the past 6 months.
Interventions
N=69 alteplase (intravenous loading dose of 0.3 mg/kg or 0.6 mg/kg over 2 hours followed by daily long-term infusion of 0.02 mg/kg/h or 0.04 mg/kg/h over 5 days plus standard of care).
N=35 standard of care (best possible treatment regimen established locally).
Primary outcome
Median time to clinical improvement up to day 28
25 days
28 days
28.0 days
21.0 days
14.0 days
7.0 days
0.0 days
Alteplase
Standard of
care
No significant
difference ↔
No significant difference in median time to clinical improvement up to day 28 (25 days vs. 28 days; HR 1.23, 95% CI 0.67 to 2.27).
Secondary outcomes
No significant difference in the rate of treatment failure up to day 28 (39% vs. 49%; ARD -8, 95% CI -27 to 12).
No significant difference in the rate of death up to day 28 (12% vs. 29%; HR 0.42, 95% CI 0.16 to 1.1).
No significant difference in mean length of hospital stay up to day 28 (23 days vs. 24.4 days; MD -1, 95% CI -4 to 2).
Safety outcomes
No significant difference in adverse and serious adverse events.
Significant difference in major bleeding event up to day 6 (13% vs. 0%).
Conclusion
In patients with COVID-19-associated severe hypoxemic respiratory failure, alteplase was not superior to standard of care with respect to median time to clinical improvement up to day 28.
Reference
Giovanni Landoni, Pratima Chowdary, Ferhat Meziani et al. Alteplase in COVID-19 severe hypoxemic respiratory failure: the TRISTARDS multicenter randomized trial. Ann Intensive Care. 2024 Nov 10;14(1):170.
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