FREEDOM COVID-19 Anticoagulation Strategy

NCT04512079 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: GCO 20-2115
• Study Type: interventional
• Target: 3,460
• Locations: 5 countries
• Sites: 21

Brief Summary

Coronavirus Disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to unprecedented morbidity and mortality in the modern era. To date, nearly 13 million people have contracted COVID-19, leading to more than 550,000 deaths worldwide. As the number of affected individuals continues to climb, effective strategies for treatment and prevention of the disease are of paramount importance. SARS-CoV-2 is understood to directly invade cells via the human angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed predominantly in the lungs but also throughout the cardiovascular system. Thus, while acute respiratory distress syndrome remains a feared complication, new thromboembolic disease has emerged as a common and potentially catastrophic manifestation of COVID-19.

Conditions

COVID-19; SARS-CoV-2

Keywords

Randomization; Hospitalization; PCR or Antigen Positive Test; Abnormal Laboratory Maker; Anticoagulation; Apixaban

Outcome Measures

Primary Outcomes (2)

• Time to first event

  The time to first event rate within 30 days of randomization of the composite of all-cause mortality, intubation requiring mechanical ventilation, systemic thromboembolism (including pulmonary emboli) confirmed by imaging or requiring surgical intervention OR ischemic stroke confirmed by imaging.

  30 days

• Number of in-hospital rate of BARC 3 or 5

  Number of in-hospital rate of BARC 3 or 5 bleeding (binary). BARC Type 3: a. Overt bleeding plus hemoglobin drop of 3 to \< 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding b. Overt bleeding plus hemoglobin drop \< 5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents c. Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision. BARC Type 5: 1. Probable fatal bleeding 2. Definite fatal bleeding (overt or autopsy or imaging confirmation)

  30 days

Secondary Outcomes (16)

• Number of participants with Myocardial infarction

  30 days after randomization

• Number of participants with Myocardial infarction

  90 days after randomization

• Number of participants with Deep Vein Thrombosis

  30 days after randomization

• Number of participants with Deep Vein Thrombosis

  90 days after randomization

• Number of participants requiring Ventilation

  30 after randomization

Study Arms (3)

Prophylactic Enoxaparin

ACTIVE COMPARATOR

Prophylactic enoxaparin (40 mg SC QD; 30 mg SC QD for CrCl \<30 mL/min)

Drug: Enoxaparin

Full Dose Enoxaparin

ACTIVE COMPARATOR

Full-dose enoxaparin (1 mg/kg SC Q12h; 1 mg/kg SC QD for CrCl \<30 mL/min)

Drug: Enoxaparin

Apixaban

EXPERIMENTAL

Apixaban (5 mg Q12h; 2.5 mg Q12h for patients with at least two of three of age ≥80 years, weight ≤60 kg or serum creatinine ≥1.5 mg/dL)

Drug: Apixaban

Interventions

Enoxaparin DRUG

Prophylactic enoxaparin (40 mg SC QD; 30 mg SC QD for CrCl \<30 mL/min) Full-dose enoxaparin (1 mg/kg SC Q12h; 1 mg/kg SC QD for CrCl \<30 mL/min)

Full Dose Enoxaparin; Prophylactic Enoxaparin

Apixaban DRUG

(5 mg Q12h; 2.5 mg Q12h for patients with at least two of three of age ≥80 years, weight ≤60 kg or serum creatinine ≥1.5 mg/dL)

Apixaban

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalization within the prior 24 hours 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 degrees Celsius
• O2 saturation ≤94
• Abnormal laboratory marker (at least 1):
• i. d-dimer ≥1.0 μg /mL ii. CRP \>2 mg/L iii. Ferritin \>300 μg /L iv. Lymphopenia \<1500 cells /m3
• Patient or legal guardian provides written informed consent

You may not qualify if:

• Age \<18 years
• Mechanical ventilation on admission or high likelihood for the need for invasive mechanical ventilation within 24 hours of admission
• Anticipated duration of hospital stay \<72 hours
• Treatment with therapeutic dose UFH or LMWH, vitamin K antagonists, or NOACs within seven 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 central nervous system
• intracranial malignancy
• history of intracranial bleeding
• history of bleeding diatheses (e.g., hemophilia)
• history of gastrointestinal bleeding within previous 3 months
• thrombolysis within the previous 7 days
• presence of an epidural or spinal catheter

Sponsors & Collaborators

• Valentin Fuster: lead

Study Sites (21)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Instituto do Coração - INCOR

São Paulo, Brazil

Location

Instituto Prevent Senior - IPS

São Paulo, Brazil

Location

Clínica de la Costa

Barranquilla, Colombia

Location

Clínica Shaio

Bogotá, Colombia

Location

Fundación Cardioinfantil

Bogotá, Colombia

Location

Fundacion Oftalmológica de Santander - Foscal

Bucaramanga, Colombia

Location

Centro Médico Imbanaco

Cali, Colombia

Location

CardioVid

Medellín, Colombia

Location

Eternal Heart Care Centre and Research Ins Pvt Ltd.

Jaipur, India

Location

Jaipur National University

Jaipur, India

Location

Sawai Mann Singh Hospital

Jaipur, India

Location

Jaslok Hospital & Research Center

Mumbai, India

Location

Saifee Hospital

Mumbai, India

Location

Sengupta Hospital & Research Institute

Nagpur, India

Location

D Y Patil University School of Medicine & D Y Patil Hospital

Navi Mumbai, India

Location

Hospital Cardiológica Aguascalientes

Aguascalientes, Mexico

Location

Centro Médico Nacional 20 de Noviembre

Mexico City, Mexico

Location

Christus Muguerza Hospital Alta Especialidad

Monterrey, Mexico

Location

Centro de Estudios Clinicos de Querétaro S.C.

Querétaro City, Mexico

Location

Centro Medico Hospital del Prado

Tijuana, Mexico

Location

Related Publications (2)

• Stone GW, Farkouh ME, Lala A, Tinuoye E, Dressler O, Moreno PR, Palacios IF, Goodman SG, Esper RB, Abizaid A, Varade D, Betancur JF, Ricalde A, Payro G, Castellano JM, Hung IFN, Nadkarni GN, Giustino G, Godoy LC, Feinman J, Camaj A, Bienstock SW, Furtado RHM, Granada C, Bustamante J, Peyra C, Contreras J, Owen R, Bhatt DL, Pocock SJ, Fuster V; FREEDOM COVID Anticoagulation Strategy Randomized Trial Investigators. Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19. J Am Coll Cardiol. 2023 May 9;81(18):1747-1762. doi: 10.1016/j.jacc.2023.02.041. Epub 2023 Mar 6.

  PMID: 36889611 DERIVED

• Farkouh ME, Stone GW, Lala A, Bagiella E, Moreno PR, Nadkarni GN, Ben-Yehuda O, Granada JF, Dressler O, Tinuoye EO, Granada C, Bustamante J, Peyra C, Godoy LC, Palacios IF, Fuster V. Anticoagulation in Patients With COVID-19: JACC Review Topic of the Week. J Am Coll Cardiol. 2022 Mar 8;79(9):917-928. doi: 10.1016/j.jacc.2021.12.023.

  PMID: 35241226 DERIVED

MeSH Terms

Conditions

COVID-19; Pathologic Complete Response

Interventions

Enoxaparin; apixaban

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Valentin Fuster, MD,PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Anu Lala, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Study participants will be randomized in a 1:1:1 fashion to 1 of 3 arms: 1. Prophylactic enoxaparin (40 mg SC QD; 30 mg SC QD for CrCl \<30 mL/min) 2. Full-dose enoxaparin (1 mg/kg SC Q12h; 1 mg/kg SC QD for CrCl \<30 mL/min) 3. Apixaban (5 mg Q12h; 2.5 mg Q12h for patients with at least two of three of age ≥80 years, weight ≤60 kg or serum creatinine ≥1.5 mg/dL)

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 13, 2020
• Study Start: September 8, 2020
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: March 16, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. The type of analysis that will be conducted is for individual participant data meta-analysis. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.

Locations

CO (6); US (1); IN (7); ME (5); BR (2)