NCT04512079.

Study name	FREEDOM COVID anticoagulation strategy randomized trial
Starting date	8 September 2020
Contact information	Debra Fitzpatrick, MS Icahn School of Medicine at Mount Sinai Gustave L. Levy Pl, New York, NY 10029, USA 212‐659‐9151 | debra.fitzpatrick@mssm.edu
Methods	Prospective, multicentre, open‐label, 1:1:1, 3‐armed, parallel‐assignment RCT
Participants	3600 participants, ≥ 18 years, female and male Inclusion criteria: Hospitalization within the prior 24 h for either confirmed (based on PCR or antigen‐positive test for SARS‐CoV‐2) or suspected COVID‐19 based on 3 criteria (all 3 must be present for suspected cases): Fever > 38 ºC O2 saturation ≤ 94 Abnormal laboratory marker (at least 1) D‐dimer ≥ 1.0 μg/mL CRP > 2 mg/L Ferritin > 300 μg/L Lymphopenia < 1500 cells/m³ Patient or legal guardian provides written informed consent Exclusion criteria: Age < 18 years Mechanical ventilation on admission or high likelihood for the need for invasive mechanical ventilation within 24 h of admission Anticipated duration of hospital stay < 72 h Treatment with therapeutic dose UFH or LMWH, VKA, or NOACs within 7 days Active bleeding Risk factors for bleeding, including: intracranial surgery or stroke within 3 months history of intracerebral arteriovenous malformation cerebral aneurysm or mass lesions of the CNS intracranial malignancy history of intracranial bleeding history of bleeding diatheses (e.g. haemophilia) history of GI bleeding within previous 3 months thrombolysis within the previous 7 days presence of an epidural or spinal catheter recent major surgery < 14 days uncontrolled hypertension (SBP > 200 mmHg or DBP > 120 mmHg) other physician‐perceived contraindications to anticoagulation platelet count < 50 x109/L, INR > 2.0, or baseline aPTT > 50 seconds haemoglobin < 80 g/L (to minimise the likelihood of requiring red blood cell transfusion if potential bleeding were to occur) current treatment with antithrombotics or antiplatelet agents including but not limited to ticagrelor, prasugrel, and aspirin > 100 mg, or NSAIDs (e.g. ibuprofen, naproxen, etc.) due to increased risk of bleeding, unless such agents can be permanently discontinued (aspirin ≤ 100 mg and clopidogrel ≤ 75 mg is permitted) Acute or subacute bacterial endocarditis History of HIT or other heparin allergy including hypersensitivity Patients with non‐COVID‐19‐related clinical condition for which life expectancy is < 6 months Pregnancy (women of childbearing potential are required to have a negative pregnancy test prior to enrolment) Active enrolment in other trials related to anticoagulation Patients has ESKD on chronic dialysis Patient is a member of a vulnerable population: in the judgment of the investigator the patient is unable to give informed consent for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy. This may include: Individuals with mental disability, in nursing homes, children, impoverished people, people in emergency situations, homeless people, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the sponsor, members of the armed forces, and people kept in detention
Interventions	Experimental: Apixaban (5 mg every 12 h; 2.5 mg every 12 h for patients with at least 2 of 3 of age ≥ 80 years, weight ≤ 60 kg or serum creatinine ≥ 1.5 mg/dL)  Comparator:  Prophylactic enoxaparin (40 mg SC once daily; 30 mg SC once daily for CrCl < 30 mL/min) Full‐dose enoxaparin (1 mg/kg SC every 12 h; 1 mg/kg SC once daily for CrCl < 30 mL/min)
Outcomes	Primary Time to first event (time frame: 30 days) Number of in‐hospital rate of BARC 3 or 5 (time frame: 30 days) Number of in‐hospital rate of BARC 3 or 5 bleeding (binary). BARC type 3: overt bleeding plus haemoglobin drop of 3 to < 5 g/dL (provided haemoglobin drop is related to bleed); transfusion with overt bleeding overt bleeding plus haemoglobin drop < 5 g/dL (provided haemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents intracranial haemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision. BARC type 5 Secondary Number of participants with myocardial infarction (time frame: 30 days after randomisation) Number of participants with myocardial infarction (time frame: 90 days after randomisation) Number of participants with DVT (time frame: 30 days after randomisation) Number of participants with DVT (time frame: 90 days after randomisation) Number of participants requiring ventilation (time frame: 30 after randomisation) Number of participants requiring ventilation (time frame: 90 days after randomisation) Number of all death (time frame: 30 days after randomisation) Number of all death (time frame: 90 days after randomisation) Cause of death (time frame: 30 days after randomisation) Cause of death (time frame: 90 days after randomisation) Number of participants with stroke (time frame: 30 days after randomisation) Number of participants with stroke (time frame: 90 days after randomisation) Number of participants with PE (time frame: 30 days after randomisation) Number of participants with PE (time frame: 90 days after randomisation) Number of participants with systemic thromboembolism (time frame: 30 days after randomisation) Number of participants with systemic thromboembolism (time frame: 90 days after randomisation)
Notes	NCT04512079 | No data provided