TABLE 2.
Summary of ongoing clinical trials addressing prevention strategies of thromboembolic events at the post‐acute phase of COVID‐19
| Clinical trial title/NCT | Intervention/treatment | Description | Primary outcome |
|---|---|---|---|
|
COVID‐19 Positive Outpatient Thrombosis Prevention in Adults Aged 40–80 ACTIV4 |
Apixaban 2.5 mg apixaban 5 mg Aspirin versus placebo |
Double‐blind placebo‐controlled platform trial to compare the effectiveness of anticoagulation with antiplatelet agents and with placebo to prevent thrombotic events in patients diagnosed with COVID‐19 not admitted to hospital | Hospitalization for cardiovascular/pulmonary events (time frame: 45 days) |
|
COVID‐19 Thrombosis Prevention Trials: Post‐hospital Thromboprophylaxis ACTIV4c |
Apixaban 2.5 mg versus placebo | Adaptive, prospective, randomized platform Phase III trial designed to compare the effectiveness and safety of antithrombotic therapy with no antithrombotic therapy after hospitalization for 48 h 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). | 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) |
|
Medically Ill Hospitalized Patients for COVID‐19 THrombosis Extended ProphyLaxis With Rivaroxaban ThErapy THe MICHELLE Trial |
Rivaroxaban 10 mg versus no intervention after discharge | Randomized Phase III trial evaluating the safety and efficacy of rivaroxaban 10 mg OD for 35 ± 4 days versus no intervention after hospital discharge in COVID‐19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization |
Venous thromboembolism (VTE) and VTE related‐death (time frame: at day 35 ± post hospital discharge). A composite efficacy end point of symptomatic VTE, VTE‐related death, and/or VTE detected by mandatory bilateral lower limb venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 post hospital discharge |
|
Effect of Anticoagulation Therapy on Clinical Outcomes in COVID‐19 COVID‐PREVENT |
Rivaroxaban versus standard of care | Multicenter, prospective, randomized, Phase II, event‐driven study. Thromboprophylaxis therapy will be given for 28 days up to day 35 post randomization or even longer. If the patient cannot be discharged from the hospital prior to day 35 post randomization, the thromboprophylaxis phase will also start upon hospital discharge, but is then shorter than 28 days, because the study ends at day 60 post randomization | Composite end point of venous thromboembolism (DVT and/or fatal or non‐fatal PE), arterial thromboembolism, new myocardial infarction, non‐hemorrhagic stroke, all‐cause mortality or progression to intubation and invasive ventilation (time frame: 35 days post randomization) |
|
Effect of the Use of Anticoagulant Therapy During Hospitalization and Discharge in Patients With COVID‐19 Infection XACT |
Enoxaparine (prophylactic or therapeutic dose) |
Randomized clinical trial in patients with confirmed COVID‐19 who require hospital treatment and subsequent ambulatory surveillance |
Identifying the benefit of different doses of low‐molecular‐weight heparin (enoxaparin) on ventilatory support time, length of hospital stay, and mortality in patients requiring hospital care for COVID‐19 infection. Comparing oral anticoagulation therapy by administering rivaroxaban 10 mg PO every 24 h on early thrombotic complications |
|
Hamburg Edoxaban for Anticoagulation in COVID‐19 Study (HERO‐19) |
Edoxaban and/or high‐dose LMWH versus low‐dose low‐molecular‐weight heparin or placebo | Prospective, randomized, assessor‐blinded, multicenter, placebo‐controlled, interventional Phase III trial that will investigate whether therapeutic anticoagulation on top of SOC compared to prophylactic anticoagulation as part of SOC can improve objective patient‐relative end points, relevant for prognosis in patients with COVID‐19 |
All‐cause mortality and/or venous/arterial thromboembolism (time frame: 42 days) All‐cause mortality and/or venous/arterial thromboembolism during follow‐up (42 days). Thromboembolisms will be detected by duplex ultrasonography of arms and legs |
|
A Study of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic Coronavirus Disease 2019 (COVID‐19) Infection PREVENT‐HD trial (NCT04508023) |
Rivaroxaban versus placebo |
Multicenter, randomized, placebo‐controlled, pragmatic Phase III study investigating the efficacy and safety of rivaroxaban to reduce the risk of major venous and arterial thrombotic events, hospitalization, and eeath in medically ill outpatients with acute, symptomatic COVID‐19 infection. |
Time to first occurrence of a composite end point of symptomatic venous thromboembolism (VTE), myocardial infarction (MI), ischemic stroke, acute limb ischemia, noncentral nervous system (non‐CNS) systemic embolization, all‐cause hospitalization, and all‐cause mortality will be assessed (time frame up to day 35) |
|
Protective Effect of Aspirin on COVID‐19 Patients (PEAC) |
Aspirin 100 mg | Randomized, parallel‐assignment, open label, Phase II–III trial, assessing the early use of aspirin in COVID‐19 patients, which has the effects of inhibiting virus replication, antiplatelet aggregation, anti‐inflammatory and anti‐lung injury, is expected to reduce the incidence of severe and critical patients, shorten the length of hospital duration, and reduce the incidence of cardiovascular complications. | Clinical recovery time (TTCR) (time frame: not more than 14 days) |
|
Aggrenox To Treat Acute Covid‐19 (ATTAC‐19) ATTAC‐19 |
Dipyridamole ER 200 mg/aspirin 25 mg orally/enterally AND SOC vs. SOC | Randomized controlled trial to evaluate the outcomes with aggrenox in patients with SARS‐CoV‐2 infection | Change in composite COVID ordinal scale at day 15 |