Enoxaparin for thromboprophylaxis in hospitalized COVID‐19 patients: The X‐COVID‐19 Randomized Trial

• DOI: 10.1111/eci.13735
• Publication Date: 2021-12-27T06:24:32Z
• Authors: Nuccia Morici; GianMarco Podda; Simone Birocchi; Luca Bonacchini; Marco Merli; Michele Trezzi; Gianluca Massaini; Marco Agostinis; Giulia Carioti; Francesco Saverio...; Gianluca Gazzaniga; Daniela Barberis; Laura Antolini; Maria Grazia Vals...; Marco Cattaneo
• Keywords: COVID-19; enoxaparin; pulmonary embolism; thrombosis; Anticoagulants; COVID-19; Hemorrhage; Venous Thromboembolism; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Humans; Enoxaparin; Pulmonary Embolism; COVID-19; enoxaparin; pulmonary embolism; thrombosis

AbstractBackgroundIt is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID‐19 patients hospitalized in general wardsMethodsThis is a multicentre, open‐label, randomized trial performed in 9 Italian centres, comparing 40 mg b.i.d. versus 40 mg o.d. enoxaparin in COVID‐19 patients, between April 30 2020 and April 25 2021. Primary efficacy outcome was in‐hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding.ResultsThe study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6.5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (ARR 6.5, 95% CI: 1.5–11.6). The absence of concomitant DVT and imaging characteristics suggests that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically nonsignificant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm.ConclusionsNo DVT developed in COVID‐19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events.