COVID-19
Conditions
Brief summary
A multi-center adaptive randomized placebo-controlled platform trial evaluating the efficacy and safety of anti-thrombotic strategies in COVID-19 adults not requiring hospitalization at time of diagnosis
Detailed description
The COVID-19 Outpatient Thrombosis Prevention Trial is a multi-center adaptive randomized double-blind placebo-controlled platform trial to compare the effectiveness of anti-coagulation with anti-platelet agents and with placebo to prevent thrombotic events in patients diagnosed with COVID-19 who have evidence of increased inflammation based on elevated D-dimer and hsCRP levels, yet are not admitted to hospital as COVID-19 related symptoms are currently stable. Participants will all be adults between 40 and 79 years who will be enrolled from approximately 100 facilities, such as emergency rooms and other settings where a physician is present to evaluate the patient for inclusion and exclusion criteria.
Interventions
Subjects will be contacted either electronically or by telephone within 24 hours of randomization to confirm receipt of the study treatment. Study drug will be shipped to subjects home. Subjects will take Apixaban 2.5 MG twice a day; once in the morning and once in the evening for 45 days. Subjects will be contacted (electronic or telephone) minimally weekly after initial start of study medication and contact will continue up to day 75 after starting study treatment. Follow up electronic contact will be dependent on initial patient response, compliance with response, and medication adherence, for the trial duration using electronic contacts and through telephone contacts. Participants will be queried for any clinically relevant endpoints, especially major bleeding, or need to seek healthcare attention for any reason. Follow-up will occur from the time of study drug receipt and through the 30 day safety period.
Subjects will be contacted either electronically or by telephone within 24 hours of randomization to confirm receipt of the study treatment. Study drug will be shipped to subjects home. Subjects will take Apixaban 5 MG twice a day; once in the morning and once in the evening for 45 days. Subjects will be contacted (electronic or telephone) minimally weekly after initial start of study medication and contact will continue up to day 75 after starting study treatment. Follow up electronic contact will be dependent on initial patient response, compliance with response, and medication adherence, for the trial duration using electronic contacts and through telephone contacts. Participants will be queried for any clinically relevant endpoints, especially major bleeding, or need to seek healthcare attention for any reason. Follow-up will occur from the time of study drug receipt and through the 30 day safety period.
Subjects will be contacted either electronically or by telephone within 24 hours of randomization to confirm receipt of the study treatment. Study drug will be shipped to subjects home. Subjects will take Aspirin twice a day; once in the morning and once in the evening for 45 days. Subjects will be contacted (electronic or telephone) minimally weekly after initial start of study medication and contact will continue up to day 75 after starting study treatment. Follow up electronic contact will be dependent on initial patient response, compliance with response, and medication adherence, for the trial duration using electronic contacts and through telephone contacts. Participants will be queried for any clinically relevant endpoints, especially major bleeding, or need to seek healthcare attention for any reason. Follow-up will occur from the time of study drug receipt and through the 30 day safety period.
Subjects will be contacted either electronically or by telephone within 24 hours of randomization to confirm receipt of the study treatment. Study placebo will be shipped to subjects home. Subjects will take placebo twice a day; once in the morning and once in the evening for 45 days. Subjects will be contacted (electronic or telephone) minimally weekly after initial start of study medication and contact will continue up to day 75 after starting study treatment. Follow up electronic contact will be dependent on initial patient response, compliance with response, and medication adherence, for the trial duration using electronic contacts and through telephone contacts. Participants will be queried for any clinically relevant endpoints, especially major bleeding, or need to seek healthcare attention for any reason. Follow-up will occur from the time of study drug receipt and through the 30 day safety period.
Sponsors
Study design
Masking description
Double-blind
Eligibility
Inclusion criteria
Inclusion: * COVID-19+ in past 14 days * Platelets \> 100,000 * eGFR \> 30ml/min Exclusion: * Hospitalized * Contradiction/ other indication for anti-coagulation * Pregnancy * Active cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization for Cardiovascular/Pulmonary Events | 45 days | The primary outcome will be a composite endpoint of need for hospitalization for cardiovascular/pulmonary events, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality for up to 45 days after initiation of assigned treatment. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from a variety of different facilities where (a) a clinician can evaluate the patient for inclusion and exclusion criteria, and (b) where blood samples can be arranged to be sent for D-dimer, hsCRP, calculated creatinine clearance, and platelet count. COVID-19 testing needs to be confirmed positive within the past 14 days. Serum or urine pregnancy test results will be required for women of childbearing potential before starting study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban 2.5mg Anticoagulation: prophylactic dose Apixaban 2.5mg po bid | 165 |
| Apixaban 5mg Anticoagulation: therapeutic dose Apixaban 5.0mg po bid | 164 |
| Asprin Antiplatelet agent: low dose aspirin 81mg po qd | 164 |
| Placebo Only Placebo | 164 |
| Total | 657 |
Baseline characteristics
| Characteristic | Apixaban 2.5mg | Total | Placebo | Asprin | Apixaban 5mg |
|---|---|---|---|---|---|
| Age, Continuous | 55 years | 52 years | 54 years | 54 years | 52 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 9 Participants | 2 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 78 Participants | 16 Participants | 20 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 69 Participants | 14 Participants | 22 Participants | 18 Participants |
| Race (NIH/OMB) White | 124 Participants | 494 Participants | 131 Participants | 119 Participants | 120 Participants |
| Region of Enrollment United States | 165 participants | 657 participants | 164 participants | 164 participants | 164 participants |
| Sex: Female, Male Female | 95 Participants | 388 Participants | 96 Participants | 95 Participants | 102 Participants |
| Sex: Female, Male Male | 70 Participants | 269 Participants | 68 Participants | 69 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 165 | 0 / 164 | 0 / 164 | 0 / 164 |
| other Total, other adverse events | 9 / 165 | 13 / 164 | 6 / 164 | 3 / 164 |
| serious Total, serious adverse events | 0 / 165 | 0 / 164 | 0 / 164 | 0 / 164 |
Outcome results
Hospitalization for Cardiovascular/Pulmonary Events
The primary outcome will be a composite endpoint of need for hospitalization for cardiovascular/pulmonary events, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality for up to 45 days after initiation of assigned treatment.
Time frame: 45 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5mg | Hospitalization for Cardiovascular/Pulmonary Events | 1 participants |
| Apixaban 5mg | Hospitalization for Cardiovascular/Pulmonary Events | 1 participants |
| Asprin | Hospitalization for Cardiovascular/Pulmonary Events | 0 participants |
| Placebo | Hospitalization for Cardiovascular/Pulmonary Events | 0 participants |