Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection
Status:
Active, not recruiting
Trial end date:
2021-11-01
Target enrollment:
Participant gender:
Summary
The global pandemic COVID-19 has overwhelmed the medical capacity to accommodate a large
surge of patients with acute respiratory distress syndrome (ARDS). In the United States, the
number of cases of COVID-19 ARDS is projected to exceed the number of available ventilators.
Reports from China and Italy indicate that 22-64% of critically ill COVID-19 patients with
ARDS will die. ARDS currently has no evidence-based treatments other than low tidal
ventilation to limit mechanical stress on the lung and prone positioning. A new therapeutic
approach capable of rapidly treating and attenuating ARDS secondary to COVID-19 is urgently
needed.
The dominant pathologic feature of viral-induced ARDS is fibrin accumulation in the
microvasculature and airspaces. Substantial preclinical work suggests antifibrinolytic
therapy attenuates infection provoked ARDS. In 2001, a phase I trial 7 demonstrated the
urokinase and streptokinase were effective in patients with terminal ARDS, markedly improving
oxygen delivery and reducing an expected mortality in that specific patient cohort from 100%
to 70%. A more contemporary approach to thrombolytic therapy is tissue plasminogen activator
(tPA) due to its higher efficacy of clot lysis with comparable bleeding risk 8. We therefore
propose a phase IIa clinical trial with two intravenous (IV) tPA treatment arms and a control
arm to test the efficacy and safety of IV tPA in improving respiratory function and
oxygenation, and consequently, successful extubation, duration of mechanical ventilation and
survival.
Phase:
Phase 2
Details
Lead Sponsor:
Denver Health and Hospital Authority
Collaborators:
Ben Taub Hospital Beth Israel Deaconess Medical Center Genentech, Inc. Genentech, Inc., University of Colorado Denver, National Jewish, Beth Israel Deaconess Medical Center, and Long Island Jewish Hospital Long Island Jewish Medical Center Methodist Dallas Medical Center National Jewish Health Scripps Health St. Mary's Medical Center University of Colorado, Denver University of Miami