Clinical trial NCT04516941: CorONa Virus edoxabaN ColchicinE (CONVINCE) COVID-19
Official title: Efficacy and Safety of Edoxaban and or Colchicine for Patients With SARS-CoV-2 Infection Managed in the Out of Hospital Setting
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: SARS-CoV Infection
COVID-19
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
First posted: 2020-08-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 2x2 factorial design
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Edoxaban vs. no active treatment
timeFrame: Baseline to day 25
measure: Colchicine vs no active treatment
timeFrame: Baseline to day 14
Secondary outcomes:
measure: Number of patients with asymptomatic proximal deep-vein thrombosis
timeFrame: Baseline to day 25
measure: Number of patients with symptomatic proximal or distal deep-vein thrombosis
timeFrame: Baseline to day 25
measure: Number of patient with symptomatic pulmonary embolism or thrombosis
timeFrame: Baseline to day 25
measure: Number of patients with myocardial infarction
timeFrame: Baseline to day 25
measure: Number of patients with ischemic stroke
timeFrame: Baseline to day 25
measure: Number of patients with non-CNS systemic embolism
timeFrame: Baseline to day 25
measure: Number of deaths
timeFrame: Baseline to day 25
measure: Ventilation need
timeFrame: Baseline to day 25
Other outcomes:
Locations:
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Garbagnate Milanese
country: Italy
facility: ASST Rhodense
city: Milan
country: Italy
facility: ASST Grande Ospedal Metropolitano Niguardia
city: Lugano
country: Switzerland
facility: Ospedale regionale Lugano
state: Ticino
city: Bern
country: Switzerland
facility: Bern University Hospital
Study officials:
affiliation: Bern University Hospital
name: Stephan Windecker, Prof. Dr.
role: STUDY_CHAIR
References:
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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. J Thromb Haemost. 2020 Jul;18(7):1738-1742. doi: 10.1111/jth.14850. Epub 2020 Jun 24.
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 14;142(2):184-186. doi: 10.1161/CIRCULATIONAHA.120.047430. Epub 2020 Apr 24. No abstract available.
citation: Mikolajewska A, Fischer AL, Piechotta V, Mueller A, Metzendorf MI, Becker M, Dorando E, Pacheco RL, Martimbianco ALC, Riera R, Skoetz N, Stegemann M. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD015045. doi: 10.1002/14651858.CD015045.