Apixaban for PrOphyLaxis of thromboemboLic Outcomes in COVID-19

Conditions

Covid19, Thrombosis

Keywords

SARS-CoV2, Anticoagulation, Apixaban

Brief summary

Randomized, double-blinded, placebo-controlled trial comparing oral anticoagulation with placebo for community-dwelling patients with symptomatic COVID-19 infection and risk factors for thrombosis.

Detailed description

Randomized, double-blinded, placebo-controlled trial comparing oral anticoagulation with placebo for community-dwelling patients with symptomatic COVID-19 infection and risk factors for thrombosis. Randomization 1:1 - Group 1 will receive Apixaban 2.5mg twice daily vs. matching placebo (Group 2) for 30 days. Primary Objective: To evaluate the clinical impact of a strategy of oral anticoagulation with apixaban comparing with placebo on the number of days alive and out of the hospital/emergency department (DAOH) through 30 days in outpatients with symptomatic SARS-CoV2 infection and risk factors for thrombosis.

Barco S, Voci D, Held U, Sebastian T, Bingisser R, Colucci G, Duerschmied D, Frenk A, Gerber B, Götschi A, Konstantinides SV, Mach F, Robert-Ebadi H, Rosemann T, Simon NR, Spechbach H, Spirk D, Stortecky S, Vaisnora L, Righini M, Kucher N, OVID investigators.

2022-06-3043 citations

10.1016/s2352-3026(22)00175-2

Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.

Ramacciotti E, Barile Agati L, Calderaro D, Aguiar VCR, Spyropoulos AC, de Oliveira CCC, Lins Dos Santos J, Volpiani GG, Sobreira ML, Joviliano EE, Bohatch Júnior MS, da Fonseca BAL, Ribeiro MS, Dusilek C, Itinose K, Sanches SMV, de Almeida Araujo Ramos K, de Moraes NF, Tierno PFGMM, de Oliveira ALML, Tachibana A, Chate RC, Santos MVB, de Menezes Cavalcante BB, Moreira RCR, Chang C, Tafur A, Fareed J, Lopes RD, MICHELLE investigators.

2021-12-15177 citations

10.1016/s0140-6736(21)02392-8

Interventions

DRUGApixaban 2.5 MG

Apixaban 2.5mg twice daily for 30 days

DRUGPlacebo

placebo twice daily for 30 days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Outpatients with symptomatic laboratory-proven diagnosis of COVID-19 (any exam that shows acute infection as positive PCR or IgM in a context of acute symptoms ≤ 10 days) AND * Negative pregnancy test for women in child bearing period AND * D-dimer level ≥ 2x ULN or * C-reactive protein (CRP) ≥ 10 mg/L or * At least two of the following risk factors: * d-dimer level ≥ULN * CRP ≥ULN * age ≥65, * diabetes, * chronic kidney disease stage 3 * cardiopulmonary disease (for example, peripheral arterial disease, coronary artery disease, heart failure, chronic obstructive pulmonary disease), * history of PE/DVT, * nursing home/SNF resident or severely restricted mobility * Body mass index ≥30 kg/m2.

Exclusion criteria

* Age \< 18 years-old * Patients with indication for full anticoagulation during inclusion (for example, diagnosis of venous thromboembolism, atrial fibrillation, mechanical valve prosthesis) * Platelets \< 50,000 /mm3 * Use of acetylsalicylic acid \> 100 mg per day * Use of P2Y12 inhibitor (clopidogrel, prasugrel, ticagrelor) * Chronic use of NSAIDs * Hypersensitivity to apixaban * Creatinine clearance \< 30 ml/min * Pregnancy or breastfeeding * Patients contraindicated to anticoagulation (active bleeding, recent major surgery, blood dyscrasia or prohibitive hemorrhage risk as evaluated by the investigator) * A history of hemorrhagic stroke or any intracranial bleeding at any time in the past or current intracranial neoplasm (benign or malignant), cerebral metastases, arteriovenous (AV) malformation, or aneurysm * Use of strong inhibitors of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) (e.g. protease inhibitors, ketoconazole, Itraconazole) and/or use of P-gp and strong CYP3A4 inducers (such as but not limited to rifampin/rifampicin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, or St. John's Wort)

Design outcomes

Primary

Measure	Time frame	Description
Number of days alive and out of hospital or emergency department	In 30 days	Number of days alive and out of hospital or emergency department through 30 days.

Secondary

Measure	Time frame	Description
Hospitalizations for cardiopulmonary causes	In 30 days	—
All-cause hospitalization	In 30 days	—
Hospitalization due to bleeding	In 30 days	—
Days free of venous thromboembolism	In 30 days	Venous thromboembolism (VTE) include deep venous thrombosis and pulmonary embolism.
Major cardiovascular events (MACE)	In 30 days	Major cardiovascular events (MACE) includes cardiovascular death, myocardial infarction (MI) and stroke.
All-cause death	In 30 days	—

Countries

Brazil

Outcome results

None listed