CorONa Virus edoxabaN ColchicinE (CONVINCE) COVID-19

NCT04516941 | Terminated Phase 3 DMC

• 1 other identifier: CONVINCE Version 1.0 12052020
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 5

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.

Conditions

SARS-CoV Infection; COVID-19

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (8)

• Number of patients with asymptomatic proximal deep-vein thrombosis

  Baseline to day 25

• Number of patients with symptomatic proximal or distal deep-vein thrombosis

  Baseline to day 25

• Number of patient with symptomatic pulmonary embolism or thrombosis

  Baseline to day 25

• Number of patients with myocardial infarction

  Baseline to day 25

• Number of patients with ischemic stroke

  Baseline to day 25

Study Arms (4)

Edoxaban

ACTIVE COMPARATOR

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

Colchicine

ACTIVE COMPARATOR

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

No Edoxaban and No Colchicine

NO INTERVENTION

No intervention

Edoxaban and Colchicine

ACTIVE COMPARATOR

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; Drug: Colchicine Tablets

Interventions

Edoxaban Tablets DRUG

Treatment

Edoxaban; Edoxaban and Colchicine

Colchicine Tablets DRUG

Treatment

Colchicine; Edoxaban and Colchicine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) who are managed at home or in another out-of-hospital setting.

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company: collaborator

Study Sites (5)

Jessa Ziekenhuis

Hasselt, 3500, Belgium

Location

ASST Rhodense

Garbagnate Milanese, 20024, Italy

Location

ASST Grande Ospedal Metropolitano Niguardia

Milan, 3, Italy

Location

Ospedale regionale Lugano

Lugano, Canton Ticino, 6900, Switzerland

Location

Bern University Hospital

Bern, 3010, Switzerland

Location

Related Publications (9)

• 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 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.

  PMID: 31986264 RESULT

• 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.

  PMID: 32073213 RESULT

• 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. No abstract available.

  PMID: 32304646 RESULT

• 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. Epub 2020 Apr 21. No abstract available.

  PMID: 32325026 RESULT

• 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.14854. Epub 2020 May 6.

  PMID: 32302448 RESULT

• 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.

  PMID: 32302438 RESULT

• 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.

  PMID: 32330083 RESULT

• Landi A, Morici N, Vranckx P, Frigoli E, Bonacchini L, Omazzi B, Tresoldi M, Camponovo C, Moccetti T, Valgimigli M. Edoxaban and/or colchicine in outpatients with COVID-19: rationale and design of the CONVINCE trial. J Cardiovasc Med (Hagerstown). 2023 Dec 1;24(12):920-930. doi: 10.2459/JCM.0000000000001556. Epub 2023 Nov 3.

  PMID: 37942793 DERIVED

• 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.

  PMID: 34658014 DERIVED

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; COVID-19

Interventions

edoxaban; Colchicine

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Stephan Windecker, Prof. Dr.

  Bern University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2x2 factorial design

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 18, 2020
• Study Start: January 21, 2021
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: September 8, 2022

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2); BE (1); IT (2)