EUCTR2020‐002234‐32‐IT.

Study name	Efficacy and safety of edoxaban and or colchicine for patients with SARS‐CoV‐2 infection managed in the out of hospital setting (COVID 19)
Starting date	28 December 2020
Contact information	Cardiologia    Freiburgstrasse, 8 3010 Bern Switzerland +41316325492 | marco.valgimigli@insel.ch
Methods	Prospective, multicentre, open‐label, 4‐armed RCT
Participants	420 participants, ≥ 18 years, female and male Inclusion criteria: Patients ≥ 18 years old with symptoms compatible with active coronavirus infection and laboratory‐confirmed SARS‐CoV‐2 infection (under RT PCR) who are managed at home or in another out‐of‐hospital setting Exclusion criteria: Hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including Child‐Pugh C cirrhosis with portal hypertension Lesion or condition, if considered to be a significant risk for major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities Uncontrolled severe hypertension Ongoing or planned treatment with parenteral or oral anticoagulants Unilateral or bilateral above‐knee, lower‐extremity amputation Inability to take oral medication or otherwise unable or unwilling to undergo/perform study‐specified procedures Have received or will receive an experimental drug or used an experimental medical device within 30 days before the planned start of treatment Pregnancy or breastfeeding or any plan to become pregnant during the study. Women (and men, for colchicine group only) with child‐bearing potential not using adequate birth control method (note: as adequate method of birth control oral contraception is recommended. If oral contraception is not feasible, both partners should use adequate barrier birth control) Need for dual anti‐platelet therapy consisting of aspirin and an oral P2Y12 inhibitor Inflammatory bowel disease or chronic diarrhoea or neuromuscular disease CrCl < 15 mL/min Anticipated use of hydroxychloroquine Participation in any other clinical trial Inability to understand the requirements of the study and to provide informed consent
Interventions	Lixiana 30 mg Edoxaban ‐ concentration unit: mg milligram(s); concentration number: 30 Colchicine Colchicine ‐ concentration unit: µg microgram(s); concentration number: 500 Lixiana 60 mg Edoxaban ‐ concentration unit: mg milligram(s); concentration number: 60
Outcomes	Primary Main objective: the aim of the CONVINCE study is therefore to assess the safety and efficacy of edoxaban and/or colchicine administration in SARS‐CoV‐2‐infected patients who are managed outside the hospital with respect to the occurrence of fatalities, hospitalisation, major vascular thrombotic events or the SARS‐CoV‐2 clearance rate under RT‐PCR Primary end point(s): this study has 2 co‐primary endpoints, one each randomisation as follows: Edoxaban vs. no active treatment Major vascular thrombotic events (MVTE) at 25 (+/‐3) days defined as a composite of: Asymptomatic proximal DVT Symptomatic proximal or distal DVT Symptomatic PE or pulmonary thrombosis Myocardial infarction Ischemic stroke Non‐CNS systemic embolism Death Colchicine vs no active treatment The SARS‐CoV‐2 detection rates at day 14 (+/‐3) under RT‐PCR or freedom from death or hospitalisation Secondary objective: not applicable Time point(s) of evaluation of this end point: 14 (+/‐3) and 25 (+/‐3) days Secondary Secondary end point(s): the secondary endpoints of the study are the following: Each component of the co‐primary endpoints Need for non‐invasive or invasive ventilation Need for oxygen therapy Body temperature kinetics Need for analgesics including NSAIDs and/or paracetamol Need for hospitalisation and total days in the hospital Any combination of the above endpoints Each component of the primary endpoint as well as pre‐specified composite endpoints at the time all SARS have come to a resolution Impact of either intervention on coagulation and inflammatory biomarkers including IL‐6, CRP, D‐dimers, sCD40L, Fibrinogen, Factor X activity and Factor XIa ECG analyses for QT segment measures and for detection of EKC changes associated to myopericarditis HsTroponin levels Bleeding endpoints according to BARC 2, 3 or 5 and ISTH major and clinically relevant non‐major bleeding
Notes	EUCTR2020‐002234‐32‐IT | No data provided | Source(s) of monetary support: Daiichi Sankyo Europe GmbH