Safety and Efficacy of Therapeutic Anticoagulation on Clinical Outcomes in Hospitalized Patients With COVID-19

• Status: Not yet recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The coronavirus disease 2019 (COVID-19) global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable morbidity and mortality in over 170 countries. Increasing age and burden of cardiovascular comorbidities are associated with a worse prognosis among patients with COVID-19. In addition, serologic markers of more severe disease including coagulation abnormalities and thrombocytopenia, are not uncommon among patients hospitalized with severe COVID-19 infection and are more common in patients who died in-hospital. As the COVID-19 pandemic continues to grow, there is a pressing need to identify safe, effective, and widely available therapies that can be scaled and rapidly incorporated into clinical practice. Understanding the putative mechanism of increased mortality risk associated with abnormal coagulation function and cardiac injury is critical to guide studies of promising therapeutic interventions. Published and anecdotal reports indicate that endothelial dysfunction and thrombosis are common in critically ill patients with COVID-19, including reports of diffuse microvascular thrombosis in the lungs, heart, liver, and kidneys. Patients with cardiovascular disease (CVD) and CVD risk factors are known to have endothelial dysfunction and a heightened risk of thrombosis. A recent study of COVID-19 inpatients from Wuhan, China observed that an elevated D-dimer level greater than 1 ug/mL was associated with an 18 times higher risk of in-hospital death, underscoring the importance of increased coagulation activity as a potential modifiable risk marker that may drive end-organ injury. Given the established link between endothelial dysfunction and thrombosis in patients with cardiovascular disease, and the association between coagulopathy and adverse outcomes in patients with sepsis, the association between increased coagulation activity, end-organ injury, and mortality risk may represent a modifiable risk factor among COVID-19 patients with critical illness. Therefore, we propose to conduct a randomized, open-label trial of therapeutic anticoagulation in COVID-19 patients with an elevated D-dimer to evaluate the efficacy and safety.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborators: Beth Israel Deaconess Medical Center; Dartmouth-Hitchcock Medical Center
• Treatments: Calcium heparin; Dalteparin; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin

Criteria

Inclusion:

• COVID-19 positive on admission or during hospitalization (having been tested within the past 5 days) with symptoms consistent with COVID-19 including fever (≥ 38C, 100.4F), pneumonia, symptoms of lower respiratory illness (e.g., cough, difficulty breathing), loss of smell or taste, myalgias, pharyngitis, or diarrhea

• Admitted to the regular medical floor or intensive care unit (ICU) without severe ARDS (P/F ratio<100)

• Elevated D-dimer (>1.5g/mL)

• Age>18 years and not older than 90

• Fibrinogen >100

• Platelets >50,000

• No prior intracranial hemorrhage or recent ischemic stroke or TIA within 6 months

• D-dimer > 1500 ng/ml

• No other clinical indication for therapeutic anticoagulation (e.g., deep vein thrombosis [DVT], pulmonary embolism [PE], atrial fibrillation, acute coronary syndromes, or extracorporeal membrane oxygenation)

Exclusion:

• Disseminated intravascular coagulation (DIC) according to the International Society on Thrombosis and Hemostasis overt DIC definition

• Hemoglobin (Hgb) <8 g/dl

• Hypersensitivity to heparin or heparin formulation including heparin-induced thrombocytopenia

• Thrombocytopenia: platelets<50,000 platelets/ul

• Uncontrolled or active/recent bleeding including intracranial hemorrhage, signs of active bleeding (e.g., blood transfusion within 30 days), any GI bleed within the past 6 months, or internal bleeding within the past 1 month

• High bleeding risk: significant closed-head or facial trauma within 3 months, traumatic or prolonged CPR (>10min), or use of dual anti-platelet therapy

• Known or suspected pregnancy

• Recent (<48 hours) or planned spinal or epidural anesthesia or puncture

• If the patient is on other anticoagulants, antihistamines, nonsteroidal anti-inflammatory drugs (i.e. aspirin) or hydroxychloroquine

• Uncontrolled hypertension