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CorONa Virus edoxabaN ColchicinE (CONVINCE) COVID-19 (CONVINCE)

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ClinicalTrials.gov Identifier: NCT04516941
Recruitment Status : Not yet recruiting
First Posted : August 18, 2020
Last Update Posted : August 18, 2020
Sponsor:
Collaborator:
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Study Description
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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.


Condition or disease Intervention/treatment Phase
SARS-CoV Infection COVID-19 Drug: Edoxaban Tablets Drug: Colchicine Tablets Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 420 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: 2x2 factorial design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Edoxaban and or Colchicine for Patients With SARS-CoV-2 Infection Managed in the Out of Hospital Setting
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Edoxaban
Edoxaban 60 mg q.d., or 30 mg q.d. in patients with CrCl = or <50 ml/min or body weight equal or less than 60 kg from randomization to end of study visit at day 25 (+/-3).
 Drug: Edoxaban Tablets
Treatment
Active Comparator: Colchicine
Colchicine at 0.5 mg per os (PO) twice daily for the first 3 days and then once daily from randomization to day 14 (+/-3) days. Treatment could be continued to day 25 (+3/-3 days).
 Drug: Colchicine Tablets
Treatment
No Intervention: No Edoxaban and No Colchicine
No intervention
Active Comparator: Edoxaban and Colchicine

Edoxaban 60 mg q.d., or 30 mg q.d. in patients with CrCl = or <50 ml/min or body weight equal or less than 60 kg from randomization to end of study visit at day 25 (+/-3).

Colchicine at 0.5 mg per os (PO) twice daily for the first 3 days and then once daily from randomization to day 14 (+/-3) days. Treatment could be continued to day 25 (+3/-3 days).

 Drug: Edoxaban Tablets
Treatment

Drug: Colchicine Tablets
Treatment


Outcome Measures
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Primary Outcome Measures :
  1. Edoxaban vs. no active treatment [ Time Frame: 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.

  2. Colchicine vs no active treatment [ Time Frame: 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 Outcome Measures :
  1. Number of patients with asymptomatic proximal deep-vein thrombosis [ Time Frame: Baseline to day 25 ]
    An intraluminal filling defect on CT scan or MR venography in the IVC or iliac veins.

  2. Number of patients with symptomatic proximal or distal deep-vein thrombosis [ Time Frame: 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.

  3. Number of patient with symptomatic pulmonary embolism or thrombosis [ Time Frame: 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


  4. Number of patients with myocardial infarction [ Time Frame: 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.

  5. Number of patients with ischemic stroke [ Time Frame: Baseline to day 25 ]
  6. Number of patients with non-CNS systemic embolism [ Time Frame: Baseline to day 25 ]
    Ischemic stroke is defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by CNS infarction

  7. Number of deaths [ Time Frame: 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

  8. Ventilation need [ Time Frame: Baseline to day 25 ]
    Need for non-invasive or invasive ventilation


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04516941


Contacts
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Contact: Stephan Windecker, Prof. Dr. +41 31 63 2 44 97 Stephan.Windecker@insel.ch
Contact: Olga Deckarm, MD +41316325492 olga.deckarm@insel.ch

Locations
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Switzerland
Bern University Hospital
Bern, Switzerland, 3010
Contact: Stephan Windecker, MD    +41316324497 ext +41316324497    Stephan.Windecker@insel.ch   
Contact: Stephan Windecker    +41316324497 ext +41316324497    Stephan.Windecker@insel.ch   
Ospedale regionale Lugano
Lugano, Switzerland, 6900
Sponsors and Collaborators
University Hospital Inselspital, Berne
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
Investigators
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Study Chair: Stephan Windecker, Prof. Dr. Bern University Hospital
More Information
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Publications of Results:

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT04516941    
Other Study ID Numbers: CONVINCE Version 1.0 12052020
First Posted: August 18, 2020    Key Record Dates
Last Update Posted: August 18, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Severe Acute Respiratory Syndrome
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Colchicine
Edoxaban
Gout Suppressants
 Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anticoagulants