The purpose of this study is to determine if therapeutic dose anticoagulation (experimental group) improves 30-day mortality in participants with COVID-19 compared to those patients receiving the intermediate dose prophylaxis (control group). Following screening, subjects will be randomized 1:1 to intermediate dose prophylaxis or therapeutic dose anticoagulation treatment arms.Treatment will continue for 28 days, followed by a 6 month follow-up period.
Drug: Enoxaparin sodium
Intermediate Dose Prophylaxis Arm:
0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min --OR-- 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 ml/min
Therapeutic Dose Anticoagulation Arm:
1 mg/kg subcutaneously every 12 hours
Other Name: Lovenox
Drug: Unfractionated heparin
Intermediate Dose Prophylaxis Arm:
7,500 units subcutaneously every 8 hours
Therapeutic Dose Anticoagulation Arm:
Dosed to target anti-Xa level 0.3 - 0.7 IU/mL or activated partial thromboplastin time (aPTT), according to institutional protocol
Other Name: Sodium heparin
Drug: Fondapariniux
Intermediate Dose Prophylaxis Arm:
2.5 mg daily subcutaneously
Therapeutic Dose Anticoagulation Arm:
Dose by weight:
If greater than or equal to 100 kg: 10 mg daily
If less than 100 kg but greater than or equal to 50 kg: 7.5 mg daily
If less than 50 kg: 5 mg daily
Other Name: Arixtra
Drug: Argatroban
Therapeutic Dose Anticoagulation Arm:
Dosed according to institutional protocol
Inclusion Criteria:
- Age >18 years old
- COVID-19 positive on (RT-PCR) nasopharyngeal swab, or suspected COVID-19 infection
with detectable SARS-CoV-2 IgG or IgM.
- Intensive care unit (ICU) patient or non-ICU patient on invasive mechanical
ventilation, BiPAP, 100% non-rebreather mask, or high flow oxygen or supplemental
oxygen of at least 4 liters per minute nasal cannula.
- D dimer level greater than 700 ng/mL (3 times the upper limit of normal).
Exclusion Criteria:
- Objectively documented deep vein thrombosis or pulmonary embolism
- Patients in whom there is very high suspicion for pulmonary embolism and are on
full-dose anticoagulation as per the treating physician
- Platelets <30,000 not due to disseminated intravascular coagulation (DIC), based on
the International Society of Thrombosis and Haemostasis (ISTH) criteria and American
Society of Hematology (ASH) Frequently Asked Questions
- Active bleeding that poses a contraindication to therapeutic anticoagulation in the
opinion of the investigator.
- History of bleeding diathesis (e.g., hemophilia, severe von Willebrand disease, severe
thrombocytopathy)
- History of intracranial hemorrhage in the last 90 days
- History of ischemic stroke in the past 2 weeks
- Major neurosurgical procedure in the past 30 days
- Cardiothoracic surgery in the past 30 days
- Intra-abdominal surgery in the past 30 days
- Intracranial malignancy
- Patients who require therapeutic anticoagulation for other reasons like atrial
fibrillation, deep venous thrombosis, pulmonary embolism, or antiphospholipid
syndrome.
New York Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York, United States
Weill Cornell Medicine
New York, New York, United States
Maria T DeSancho, MD, MSc
646-962-2065
mtd2002@med.cornell.edu
Danielle Guarneri
212-746-0974
dag2037@med.cornell.edu
Maria T DeSancho, MD, MSc, Principal Investigator
Weill Medical College of Cornell University