Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection

Completed · Phase 2

Conditions studied: Severe Acute Respiratory Syndrome, Respiratory Failure, Acute Respiratory Distress Syndrome

In brief

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.

Key facts

Study ID

NCT04357730

Run by

Denver Health and Hospital Authority

People needed

50

Starts

2020-05-14

Expected to finish

2021-09-30

Last updated by the study team

2022-01-20

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Active bleeding
• Acute myocardial infarction or history of myocardial infarction within the past 3 weeks or cardiac arrest during hospitalization
• Hemodynamic instability with Noradrenaline >0.2mcg/Kg/min
• Acute renal failure requiring dialysis
• Liver failure (escalating liver failure with total Bilirubin > 3 mg/dL)
• Suspicion of cirrhosis due to history of cirrhosis diagnosis, hepatic encephalopathy, documentation of portal hypertension, bleeding from esophageal varices, ascites, imaging or operative finding suggestive of liver cirrhosis, or constellation of abnormal laboratory test results suggestive of depressed hepatic function
• Cardiac tamponade
• Bacterial endocarditis
• Severe uncontrolled hypertension defined as SBP>185mmHg or DBP>110mmHg
• CVA (stroke), history of severe head injury within prior 3 months, or prior history of intracranial hemorrhage
• Seizure during pre-hospital course or during hospitalization for COVID-19
• Diagnosis of brain tumor, arterio-venous malformation (AVM) or ruptured aneurysm
• Currently on ECMO
• Major surgery or major trauma within the past 2 weeks
• GI or GU bleed within the past 3 weeks
• Known bleeding disorder
• P2Y12 receptor inhibitor medication (anti-platelet) within 5 days of enrollment
• Arterial puncture at a non-compressible site within the past 7 days
• Lumbar puncture within past 7 days
• Pregnancy
• INR > 1.7 (with or without concurrent use of warfarin)
• Platelet count < 100 x 109/L or history of HITT
• Fibrinogen < 300mg/dL
• Known abdominal or thoracic aneurysm
• History of CNS malignancy or CNS metastasis within past 5 years

Where it is running

• Scripps Memorial Hospital La Jolla — La Jolla, California, United States
• University of Colorado, Denver — Aurora, Colorado, United States
• Denver Health Medical Center — Denver, Colorado, United States
• National Jewish Health — Denver, Colorado, United States
• St. Mary's Medical Center — West Palm Beach, Florida, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Long Island Jewish Medical Center — New York, New York, United States
• Methodist Dallas Medical Center — Dallas, Texas, United States
• Ben Taub Hospital — Houston, Texas, United States

Full record on ClinicalTrials.gov

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