CorONa Virus edoxabaN ColchicinE (CONVINCE) COVID-19

COVID-19 Clinical Trial

— CONVINCE  

Official title:

Efficacy and Safety of Edoxaban and or Colchicine for Patients With SARS-CoV-2 Infection Managed in the Out of Hospital Setting

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04516941
• Other study ID #: CONVINCE Version 1.0 12052020
• Status: Terminated
• Phase: Phase 3
• Start date: January 21, 2021
• Est. completion date: August 31, 2022

Study information

• Verified date: August 2021
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 60
• Est. completion date: August 31, 2022
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Infections
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• Edoxaban Tablets
Treatment
• Colchicine Tablets
Treatment

Locations

Country	Name	City	State
Belgium	Jessa Ziekenhuis	Hasselt
Italy	ASST Rhodense	Garbagnate Milanese
Italy	ASST Grande Ospedal Metropolitano Niguardia	Milan
Switzerland	Bern University Hospital	Bern
Switzerland	Ospedale regionale Lugano	Lugano	Ticino

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Countries where clinical trial is conducted

Belgium,  Italy,  Switzerland, 

References & Publications (7)

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 20 — View Citation

Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, Pesenti A, Peyvandi F, Tripodi A. Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis. — View Citation

Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, Jeanpierre E, Rauch A, Labreuche J, Susen S; Lille ICU Haemostasis COVID-19 Group. Pulmonary Embolism in Patients With COVID-19: Awareness of an Increased Prevalence. Circulation. 2020 Jul — View Citation

Ranucci M, Ballotta A, Di Dedda U, Baryshnikova E, Dei Poli M, Resta M, Falco M, Albano G, Menicanti L. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020 Jul;18(7):1747-1751. doi: 10.1111/jth.14 — View Citation

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13. — View Citation

Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-1418. doi: 10.1016/S0140-6736(20)30937-5 — View Citation

Zhou F, Fan G, Liu Z, Cao B. SARS-CoV-2 shedding and infectivity - Authors' reply. Lancet. 2020 Apr 25;395(10233):1340. doi: 10.1016/S0140-6736(20)30869-2. Epub 2020 Apr 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Edoxaban vs. no active treatment	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.	Baseline to day 25
Primary	Colchicine vs no active treatment	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.	Baseline to day 14
Secondary	Number of patients with asymptomatic proximal deep-vein thrombosis	An intraluminal filling defect on CT scan or MR venography in the IVC or iliac veins.	Baseline to day 25
Secondary	Number of patients with symptomatic proximal or distal deep-vein thrombosis	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.	Baseline to day 25
Secondary	Number of patient with symptomatic pulmonary embolism or thrombosis	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	Baseline to day 25
Secondary	Number of patients with myocardial infarction	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.	Baseline to day 25
Secondary	Number of patients with ischemic stroke		Baseline to day 25
Secondary	Number of patients with non-CNS systemic embolism	Ischemic stroke is defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by CNS infarction	Baseline to day 25
Secondary	Number of deaths	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	Baseline to day 25
Secondary	Ventilation need	Need for non-invasive or invasive ventilation	Baseline to day 25