COVID-19: Post-Hospital Thromboprophylaxis A Multicenter, Adaptive, Prospective, Randomized Trial Evaluating the Efficacy and Safety of Antithrombotic Strategies in Patients with COVID-19 Following Hospital Discharge (ACTIV-4C)

This study is an adaptive, prospective, randomized trial designed to compare the effectiveness and safety of antithrombotic therapy with no antithrombotic therapy after hospitalization for 48 hours or longer for COVID-19. For Stage 1 of this study, participants will be randomized to either prophylactic anticoagulation or no anticoagulant therapy for 30 days, and then followed for an additional 60 days after the completion of treatment (total duration of follow-up, approximately 90 days). Biobanking of samples for future biomarker and mechanistic studies will be available for centers able to participate and collect samples from eligible participants. Samples will be collected at the time of enrollment and after the completion of 30 days of therapy.

• Study Weblinks:
  • Clinical Trials
• Study Design:
  • Interventional
• Study Type:
  • Clinical Trial
  • Double-Blind
  • Interventional
  • Placebo-Controlled
  • Randomized
  • Randomized Controlled Clinical Trial
• Total number of consented subjects: 1217
• Subject Sample Telemetry Report (SSTR)

• MeSH
• Clinical Trials
  • NCT04650087

Inclusion Criteria:

• Age ≥ 18 years
• COVID-19 positive test (PCR, antigen, or point of care test diagnosing a current infection) within 2 weeks of hospital admit date.
• Hospitalized for COVID-19 infection for 48 or more hours

Exclusion Criteria:

• Existing indication for anticoagulation, either therapeutic or prophylactic dose
• Contraindication to antithrombotic therapy, such as
  • Ischemic stroke, intracranial bleed, or neurosurgery within 3 months
  • Known bleeding within the last 30 days requiring emergency room presentation of hospitalization
  • Known major surgery with 14 days (at least 1 hour and/or requires general anesthesia)
  • Inherited or acquired active bleeding disorder
• Platelet count < 50,000/mcL
• Hemoglobin < 8 gm/dL
• Renal insufficiency (eGFR < 30 mL/min/1.73 m2)
• Pregnancy
• Prison inmate
• Life expectancy less than 90 days
• Unwilling or unable to provide informed consent/unwilling or unable to complete the study protocol
• Dual antiplatelet therapy that cannot be discontinued
• Concomitant need for strong inducers/inhibitors of p-gp and CYP3A4 Note that the additional exclusion criteria for dual antiplatelet therapy, and for strong inducers/inhibitors of p-gp and CYP3A4, is specific to Stage 1, since Arm A is an anticoagulant, and the anticoagulant being studied in Stage 1 is a direct oral anticoagulant.

• Primary Phenotype: COVID-19
• SARS-CoV-2
• Thrombosis
• Anticoagulant

• Study Chair
  • Thomas L. Ortel, MD, PhD. Duke University Medical Center, Durham, NC, USA.
• Study Co-Chair
  • Alison Morris, MD, MS. University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA.
• Principal Investigator
  • Tracy Y. Wang, MD, MHS, MSc. Duke University Medical Center, Durham, NC, USA.