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Background: An excessive inflammatory response and a hypercoagulable state are not infrequent in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse clinical outcomes. However, the optimal treatment strategy for COVID-19 patients managed in the out-of-hospital setting is still uncertain., Design: The CONVINCE (NCT04516941) is an investigator-initiated, open-label, blinded-endpoint, 2 × 2 factorial design randomized trial aimed at assessing two independently tested hypotheses (anticoagulation and anti-inflammatory ones) in COVID-19 patients. Adult symptomatic patients (≥18 years of age) within 7 days from reverse transcription-PCR (RT-PCR) diagnosis of SARS-CoV-2 infection managed at home or in nursery settings were considered for eligibility. Eligible patients fulfilling all inclusion and no exclusion criteria were randomized to edoxaban versus no treatment (anticoagulation hypothesis) and colchicine versus no treatment (anti-inflammatory hypothesis) in a 1 : 1:1 : 1 ratio. The study had two co-primary endpoints (one for each randomization), including the composite of major vascular thrombotic events at 25 ± 3 days for the anticoagulation hypothesis and the composite of SARS-CoV-2 detection rates at 14 ± 3 days by RT-PCR or freedom from death or hospitalizations (anti-inflammatory hypothesis). Study endpoints will be adjudicated by a blinded Clinical Events Committee. With a final sample size of 420 patients, this study projects an 80% power for each of the two primary endpoints appraised separately., Conclusion: The CONVINCE trial aims at determining whether targeting anticoagulation and/or anti-inflammatory pathways may confer benefit in COVID-19 patients managed in the out-of-hospital setting., Trial Registration: ClinicalTrials.gov number, NCT04516941., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID-19 patients hospitalized in general wards METHODS: This 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., Results: The 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., Conclusions: No 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., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)