CorONa Virus edoxabaN ColchicinE (CONVINCE) COVID-19

Insel Gruppe AG, University Hospital Bern

Status and phase: Terminated; Phase 3

Conditions: COVID-19; SARS-CoV Infection

Treatments: Drug: Edoxaban Tablets; Drug: Colchicine Tablets

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04516941

CONVINCE Version 1.0 12052020

Details and patient eligibility

About

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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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60 participants in 4 patient groups

Edoxaban

Active Comparator group

Description:

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).

Treatment:

Drug: Edoxaban Tablets

Colchicine

Active Comparator group

Description:

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).

Treatment:

Drug: Colchicine Tablets

No Edoxaban and No Colchicine

No Intervention group

Description:

No intervention

Edoxaban and Colchicine

Active Comparator group

Description:

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).

Treatment:

Drug: Edoxaban Tablets

Drug: Colchicine Tablets