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

September 2, 2022 updated by: University Hospital Inselspital, Berne

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Hasselt, Belgium, 3500
        • Jessa Ziekenhuis
  • Italy
      • Garbagnate Milanese, Italy, 20024
        • ASST Rhodense
      • Milan, Italy, 3
        • ASST Grande Ospedal Metropolitano Niguardia
  • Switzerland
      • Bern, Switzerland, 3010
        • Bern University Hospital
    • Ticino
      • Lugano, Ticino, Switzerland, 6900
        • Ospedale regionale Lugano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to day 25
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.
Baseline to day 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to day 25
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.
Baseline to day 25
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
Baseline to day 25
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.
Baseline to day 25
Number of patients with ischemic stroke
Time Frame: Baseline to day 25
Baseline to day 25
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
Baseline to day 25
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
Baseline to day 25
Ventilation need
Time Frame: Baseline to day 25
Need for non-invasive or invasive ventilation
Baseline to day 25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Investigators

  • Study Chair: Stephan Windecker, Prof. Dr., Bern University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 21, 2021

Primary Completion (Actual)

August 31, 2022

Study Completion (Actual)

August 31, 2022

Study Registration Dates

First Submitted

August 5, 2020

First Submitted That Met QC Criteria

August 17, 2020

First Posted (Actual)

August 18, 2020

Study Record Updates

Last Update Posted (Actual)

September 8, 2022

Last Update Submitted That Met QC Criteria

September 2, 2022

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CONVINCE Version 1.0 12052020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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