COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis

• ClinicalTrials.gov Identifier: NCT04650087
• Recruitment Status: Completed
• First Posted: December 2, 2020
• Last Update Posted: November 10, 2022
• Sponsor: Thomas L. Ortel
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Thomas L. Ortel, Duke University

Tracking Information

• First Submitted Date: November 30, 2020
• First Posted Date: December 2, 2020
• Last Update Posted Date: November 10, 2022
• Actual Study Start Date: February 15, 2021
• Actual Primary Completion Date: July 24, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 30, 2020): Composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality as measured by hospital records. [ Time Frame: 30 days after hospital discharge ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 1, 2022)

• The composite outcome of all-cause mortality and the EQ5D index score. [ Time Frame: 30 days after hospital discharge ]
• The composite outcome of all-cause mortality and the EQ5D index score. [ Time Frame: 90 days after hospital discharge ]
• The composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality as measured by hospital records. [ Time Frame: 45 days after hospital discharge ]
• The composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality as measured by hospital records. [ Time Frame: 90 days after hospital discharge ]
• New, symptomatic VTE (inclusive of DVT, PE, or other venous thrombosis) for up to 30 days after randomization as measured by hospital records. [ Time Frame: 30 days after randomization ]
• New, symptomatic ATE (inclusive of ischemic stroke, MI, or peripheral arterial thromboembolism) for up to 30 days after randomization as measured by hospital records. [ Time Frame: 30 days after randomization ]

Original Secondary Outcome Measures (submitted: November 30, 2020)

• The composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality as measured by hospital records. [ Time Frame: 45 days after hospital discharge ]
• The composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality as measured by hospital records. [ Time Frame: 90 days after hospital discharge ]
• New, symptomatic VTE (inclusive of DVT, PE, or other venous thrombosis) for up to 30 days after randomization as measured by hospital records. [ Time Frame: 30 days after reandomization ]
• New, symptomatic ATE (inclusive of ischemic stroke, MI, or peripheral arterial thromboembolism) for up to 30 days after randomization as measured by hospital records. [ Time Frame: 30 days after randomization ]

Current Other Pre-specified Outcome Measures (submitted: July 1, 2022)

• The incidence of all-cause mortality [ Time Frame: 30 days following discharge from hospital ]
• The incidence of all-cause rehospitalization for up to 90 days after randomization [ Time Frame: 90 days following discharge from hospital ]
• The individual domains of EQ5D and the EQ5D visual analog scale for 30 and 90 days after randomization [ Time Frame: 30 and 90 days following discharge from hospital ]

Original Other Pre-specified Outcome Measures (submitted: November 30, 2020)

• The incidence of all-cause mortality [ Time Frame: 30 days following discharge from hospital ]
• The incidence of all-cause rehospitalization for up to 30 days after randomization [ Time Frame: 30 days following discharge from hospital ]

Descriptive Information

• Brief Title: COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis
• Official Title: COVID-19 Post-hospital Thrombosis Prevention Trial: An Adaptive, Multicenter, Prospective, Randomized Platform Trial Evaluating the Efficacy and Safety of Antithrombotic Strategies in Patients With COVID-19 Following Hospital Discharge
• Brief Summary: A multicenter, adaptive, randomized platform trial evaluating the efficacy and safety of antithrombotic strategies in patients with COVID-19 following hospital discharge

Detailed Description

This study is an adaptive, prospective, randomized platform 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 matching placebo for 30 days, and then followed for an additional 60 days after the completion of treatment (total duration of follow-up, 90 days).

The primary objective is to determine the most effective and safe antithrombotic strategy to prevent the composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality by 30 days following discharge from the hospital.

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 Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double Blind

Primary Purpose: Prevention

• Condition: Covid19

Intervention

• Drug: Apixaban 2.5 MG
  Participants will take Apixaban 2.5 MG twice a day, once in the morning and once in the evening for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and will continue up to day 90 after starting study treatment. Followup will occur from the time of discharge through the 30 day study period with contacts at 2 days, 10 days, 20 days and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.
  Other Name: Eliquis
• Drug: Placebo
  Participants will take placebo twice a day, once in the morning and once in the evening for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and will continue up to day 90 after starting study treatment. Followup will occur from the time of discharge through the 30 day study period with contacts at 2 days, 10 days, 20 days and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.

Study Arms

• Active Comparator: Apixaban
  Drug: Apixaban 2.5 MG Participants will be given study medication at the time of discharge from the hospital. Participants will take Apixaban 2.5 MG twice a day, once in the morning and once in the evening, for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and contact will continue up to day 90 after starting study treatment. Follow up will be through electronic and/or telephone contact depending on the participant's preference, compliance, and medication adherence. Participants will be queried for any clinically relevant endpoints, especially major bleeding or a need to seek healthcare attention for any reason. Follow-up will occur from the time of discharge and through the 30 day study period, with contacts 2 days, 10 days, 20 days, and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.
  Intervention: Drug: Apixaban 2.5 MG
• Placebo Comparator: Placebo
  Drug: Placebo Participants will be given study medication at the time of discharge from the hospital. Participants will take the Placebo twice a day, once in the morning and once in the evening, for 30 days. Participants will be contacted (electronic or telephone) 2 days after starting the study medication and contact will continue up to day 90 after starting study treatment. Follow up will be through electronic and/or telephone contact depending on the participant's preference, compliance, and medication adherence. Participants will be queried for any clinically relevant endpoints, especially major bleeding or a need to seek healthcare attention for any reason. Follow-up will occur from the time of discharge and through the 30 day study period, with contacts 2 days, 10 days, 20 days, and 30 days after discharge. Two additional study contacts will take place 45 days and 90 days after discharge.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 22, 2022): 1219
• Original Estimated Enrollment (submitted: November 30, 2020): 5320
• Actual Study Completion Date: September 23, 2022
• Actual Primary Completion Date: July 24, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• • Age ≥ 18 years

  • PCR-positive COVID-19 infection
  • Hospitalized for two or more days

Exclusion Criteria:

• Pre-existing indication for anticoagulation (e.g., pulmonary embolism or deep vein thrombosis; atrial fibrillation; mechanical cardiac valve)
• Contraindication to antithrombotic therapy (e.g., known bleeding within the last 30 days requiring emergency room presentation or hospitalization; major surgery within 14 days; ischemic stroke, intracranial bleed or neurosurgery within 3 months.
• 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 or CYP3A4

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04650087
• Other Study ID Numbers: Pro00107078
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Thomas L. Ortel, Duke University
• Original Responsible Party: Thomas Ortel, M.D., Ph.D., Duke University, Professor
• Current Study Sponsor: Thomas L. Ortel
• Original Study Sponsor: Thomas Ortel, M.D., Ph.D.
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Tracy Wang, MD; Duke University

• PRS Account: Duke University
• Verification Date: November 2022