CorONa Virus edoxabaN ColchicinE (CONVINCE) COVID-19

NCT ID: NCT04516941

Last Updated: 2022-09-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-21

Study Completion Date

2022-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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SARS-CoV Infection COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

2x2 factorial design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type ACTIVE_COMPARATOR

Edoxaban Tablets

Intervention Type DRUG

Treatment

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).

Group Type ACTIVE_COMPARATOR

Colchicine Tablets

Intervention Type DRUG

Treatment

No Edoxaban and No Colchicine

No intervention

Group Type NO_INTERVENTION

No interventions assigned to this group

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).

Group Type ACTIVE_COMPARATOR

Edoxaban Tablets

Intervention Type DRUG

Treatment

Colchicine Tablets

Intervention Type DRUG

Treatment

Interventions

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Edoxaban Tablets

Treatment

Intervention Type DRUG

Colchicine Tablets

Treatment

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

INDUSTRY

Sponsor Role collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephan Windecker, Prof. Dr.

Role: STUDY_CHAIR

Bern University Hospital

Locations

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Jessa Ziekenhuis

Hasselt, , Belgium

Site Status

ASST Rhodense

Garbagnate Milanese, , Italy

Site Status

ASST Grande Ospedal Metropolitano Niguardia

Milan, , Italy

Site Status

Ospedale regionale Lugano

Lugano, Canton Ticino, Switzerland

Site Status

Bern University Hospital

Bern, , Switzerland

Site Status

Countries

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Belgium Italy Switzerland

References

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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.

Reference Type RESULT
PMID: 31986264 (View on PubMed)

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.

Reference Type RESULT
PMID: 32073213 (View on PubMed)

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.

Reference Type RESULT
PMID: 32304646 (View on PubMed)

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.

Reference Type RESULT
PMID: 32325026 (View on PubMed)

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.

Reference Type RESULT
PMID: 32302448 (View on PubMed)

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.

Reference Type RESULT
PMID: 32302438 (View on PubMed)

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.

Reference Type RESULT
PMID: 32330083 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37942793 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34658014 (View on PubMed)

Other Identifiers

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CONVINCE Version 1.0 12052020

Identifier Type: -

Identifier Source: org_study_id

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