# Tenecteplase With Concomitant Anticoagulation for Acute Respiratory Failure in Patients With COVID-19: A Randomized Controlled Trial

## TL;DR

This study tested if tenecteplase, combined with anticoagulation, improves outcomes for patients with severe respiratory failure due to COVID-19.

## Contribution

The first randomized controlled trial to evaluate tenecteplase in treating pulmonary complications of severe COVID-19.

## Key findings

- 63% of tenecteplase-treated patients were alive and free from respiratory failure at 28 days, compared to 40% in the placebo group.
- No patients in the tenecteplase group developed renal failure, while 60% in the placebo group did.
- Mortality and major bleeding rates were similar between the two groups.

## Abstract

Background

Pulmonary thrombosis and thromboembolism play a significant role in the physiologic derangements seen in COVID-19 acute respiratory failure. The effect of thrombolysis with tenecteplase on patient outcomes is unknown.

Methods

We conducted a randomized, controlled, double-blind, phase II trial comparing tenecteplase versus placebo in patients with COVID-19 acute respiratory failure (NCT04505592). Patients with COVID-19 acute respiratory failure were randomized to tenecteplase 0.25 mg/kg or placebo in a 2:1 proportion. Both groups received therapeutic heparin for at least 72 hours.

Results

Thirteen patients were included in the trial. Eight patients were randomized to tenecteplase and five were randomized to placebo. At 28 days, 63% (n = 5) of patients assigned to the treatment group were alive and free from respiratory failure compared to 40% (n = 2) in the placebo arm (p = 0.43). Mortality at 28 days was 25% (n = 2) in the treatment arm and 20% (n = 1) in the control arm (p = 1.0). No patients in the treatment arm developed renal failure by 28 days compared to 60% (n = 3) in the placebo arm (p = 0.07). Major bleeding occurred in 25% (n = 2) of the treatment arm and 20% (n = 1) in the placebo arm; however, no patients in either arm experienced intracranial hemorrhage.

Conclusions

Tenecteplase with concomitant heparin may improve patient outcomes in patients with COVID-19 respiratory failure. As this study was limited by a small sample size, larger confirmatory studies are needed.