Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection
Severe Acute Respiratory Syndrome, Respiratory Failure, Acute Respiratory Distress Syndrome
About this trial
This is an interventional treatment trial for Severe Acute Respiratory Syndrome focused on measuring COVID-19, ARDS, SARS-CoV-2, Betacoronavirus
Eligibility Criteria
Inclusion Criteria: We will include adult patients ages 18-75 years old with known or suspected COVID-19 infection with a PaO2/FiO2 ratio < 150 or inferred PaO2/FiO2 ratio from SpO2 if ABG is unavailable (Table) persisting for > 4 hours despite optimal mechanical ventilation management according to each institution's ventilation protocols, and a neurological exam without focal signs or new deficits at time of enrollment (if patient is on paralytics, patient has been aroused sufficiently to allow a neurological examination to exclude new focal deficits or has MRI/CT scan in the last 4.5 hours with no evidence of stroke. Finally, patients must be on the ventilator for <=10 days to be eligible. Based on experience with critically ill patients, longer ventilation time may be associated with increased risk of bleeding. Patients will be enrolled based on clinical features, without consideration of language (using hospital interpreters and translated consent), race/ethnicity, or gender. A neurological exam or CT/MRI scan to demonstrate no evidence of an acute stroke is needed due to a recent case-report of large-vessel stroke as a presenting feature of COVID-19 in young individuals.
Exclusion Criteria:
- 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
- History of non-CNS malignancy within the past 5 years that commonly metastasizes to the brain (lung, breast, melanoma)
- Prisoner status
Sites / Locations
- Scripps Memorial Hospital La Jolla
- University of Colorado, Denver
- Denver Health Medical Center
- National Jewish Health
- St. Mary's Medical Center
- Beth Israel Deaconess Medical Center
- Long Island Jewish Medical Center
- Methodist Dallas Medical Center
- Ben Taub Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
No Intervention
Experimental
Experimental
Control
Alteplase-50 bolus
Alteplase-50 bolus plus drip
Patients randomized to Control arm will receive no study medication; the treatment will be standard of care according to the institution's protocol for ARDS.
Patients randomized to Alteplase-50 group will receive 50 mg of Alteplase intravenous bolus administration over 2 hours. Re-bolusing of Alteplase, at the same dose, is permitted in those patients who show an initial transient response. The repeat dose will be given between 24 and 36 hours after the initial Alteplase administration.
Patients randomized to Alteplase-50 plus drip group will receive 50 mg of Alteplase intravenous bolus administration over 2 hours. Immediately following this initial Alteplase infusion, a drip of 2 mg/hr of Alteplase will be initiated over the ensuing 24 hours (total 48 mg infusion).