SARS-CoV Infection, COVID-19
Conditions
Brief summary
There is emerging evidence that patients with SARS-CoV-2 are affected by increased coagulopathy, including in the most advanced forms, a fully blown disseminated intravascular coagulation, leading to multi organ failure (MOF). Post-Morten observations from patients who died because of SARS-CoV-2 infection in Bergamo, Italy and other places have revealed the presence of diffuse venous, arterial and microcirculatorythrombosis, not only restricted to the lung but also involving the kidneys, heart and gut. Thrombin plays a central role in mediating clot forming as well as in mediating inflammation. A direct factor X inhibitor, namely edoxaban can act as prophylactic measure to mitigate the risk of venous and arterial thrombotic complications. Colchicine is an inexpensive (generic drug), orally administered, and a potent anti-inflammatory medication. It might accelerate SARS-CoV-2 clearance. 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.
Interventions
DRUGEdoxaban Tablets
Treatment
Treatment
Sponsors
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
2x2 factorial design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with 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 breast-feeding 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 diarrhea or neuromuscular disease * Creatinine clearance (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Edoxaban vs. no active treatment | Baseline to day 25 | To assess the effect of edoxaban versus no active treatment on the composite endpoint of asymptomatic proximal deep-vein thrombosis, symptomatic proximal or distal deep-vein thrombosis, symptomatic pulmonary embolism or thrombosis, myocardial infarction, ischemic stroke, non-CNS systemic embolism or death at day 25 (+/-3) after randomization. |
| Colchicine vs no active treatment | Baseline to day 14 | To assess the effect of colchicine versus no active treatment on the SARS-CoV-2 clearance rates under RT PCR or freedom from death or hospitalisation at day 14 (+/-3) after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patient with symptomatic pulmonary embolism or thrombosis | Baseline to day 25 | Typical symptoms of PE associated with * an intra-luminal filling defect in (sub) segmental or more proximal branches on spiral computed tomography scan (CT) or computerized tomographic pulmonary angiography (CTPA). * a considerable perfusion defect (\ 75% of a segment) with a local normal ventilation result (high probability) during perfusion-ventilation lung scan (PLS, VLS or V/Q scan). * an intraluminal filling defect or a sudden cut-off of vessels (\ more than 2.5 mm in diameter) on a catheter guided pulmonary angiogram. In case of an inconclusive CTPA, inconclusive V/Q scan or inconclusive angiography demonstration of DVT in the lower extremities e.g. by compression ultrasound or venography will be required |
| Number of patients with myocardial infarction | Baseline to day 25 | For the primary analysis, MI endpoint will be defined based on the third universal definition of myocardial infarction with the exception of periprocedural MI after PCI, which will be defined according to the SCAI definition. |
| Number of patients with ischemic stroke | Baseline to day 25 | — |
| Number of patients with asymptomatic proximal deep-vein thrombosis | Baseline to day 25 | An intraluminal filling defect on CT scan or MR venography in the IVC or iliac veins. |
| Number of deaths | Baseline to day 25 | Death will be classified in 5 categories with respect to cause. Thromboembolism, cardiovascular, bleeding, Pulmonary other known cause. In general, all deaths will be assumed to be due to thromboembolism or pulmonary in nature unless another cause is obvious |
| Ventilation need | Baseline to day 25 | Need for non-invasive or invasive ventilation |
| Number of patients with non-CNS systemic embolism | Baseline to day 25 | Ischemic stroke is defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by CNS infarction |
| Number of patients with symptomatic proximal or distal deep-vein thrombosis | Baseline to day 25 | Typical symptoms of DVT associated with non-compressible vein segment on ultrasonography or an intra-luminal filling defect on venography, CT venography or MRI venography,located in the inferior vena cava (IVC), the iliac vein, the common femoral vein, the femoral or the popliteal vein. |
Countries
Belgium, Italy, Switzerland
Outcome results
None listed