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

Primary Purpose

SARS-CoV Infection, COVID-19

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Edoxaban Tablets

Colchicine Tablets

About this trial

This is an interventional treatment trial for SARS-CoV Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Jessa Ziekenhuis
ASST Rhodense
ASST Grande Ospedal Metropolitano Niguardia
Ospedale regionale Lugano
Bern University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

No Intervention

Active Comparator

Arm Label

Edoxaban

Colchicine

No Edoxaban and No Colchicine

Edoxaban and Colchicine

Arm 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).

No intervention

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).

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Number of patients with asymptomatic proximal deep-vein thrombosis

An intraluminal filling defect on CT scan or MR venography in the IVC or iliac veins.

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

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.

Number of patient with symptomatic pulmonary embolism or thrombosis

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

Number of patients with myocardial infarction

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.

Number of patients with ischemic stroke

Number of patients with non-CNS systemic embolism

Ischemic stroke is defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by CNS infarction

Number of deaths

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

Ventilation need

Need for non-invasive or invasive ventilation

Full Information

NCT ID

NCT04516941

First Posted

August 5, 2020

Last Updated

September 2, 2022

Sponsor

Insel Gruppe AG, University Hospital Bern

Collaborators

Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

1. Study Identification

Unique Protocol Identification Number

NCT04516941

Brief Title

CorONa Virus edoxabaN ColchicinE (CONVINCE) COVID-19

Acronym

CONVINCE

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

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Terminated

Why Stopped

Insufficient rate of patient accrual and newly available scientific evidence

Study Start Date

January 21, 2021 (Actual)

Primary Completion Date

August 31, 2022 (Actual)

Study Completion Date

August 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Insel Gruppe AG, University Hospital Bern

Collaborators

Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

SARS-CoV Infection, COVID-19

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Factorial Assignment

Model Description

2x2 factorial design

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Edoxaban

Arm Type

Active Comparator

Arm 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).

Arm Title

Colchicine

Arm Type

Active Comparator

Arm 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).

Arm Title

No Edoxaban and No Colchicine

Arm Type

No Intervention

Arm Description

No intervention

Arm Title

Edoxaban and Colchicine

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Edoxaban Tablets

Intervention Description

Treatment

Intervention Type

Drug

Intervention Name(s)

Colchicine Tablets

Intervention Description

Treatment

Primary Outcome Measure Information:

Title

Edoxaban vs. no active treatment

Description

Time Frame

Baseline to day 25

Title

Colchicine vs no active treatment

Description

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.

Time Frame

Baseline to day 14

Secondary Outcome Measure Information:

Title

Number of patients with asymptomatic proximal deep-vein thrombosis

Description

An intraluminal filling defect on CT scan or MR venography in the IVC or iliac veins.

Time Frame

Baseline to day 25

Title

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

Description

Time Frame

Baseline to day 25

Title

Number of patient with symptomatic pulmonary embolism or thrombosis

Description

Time Frame

Baseline to day 25

Title

Number of patients with myocardial infarction

Description

Time Frame

Baseline to day 25

Title

Number of patients with ischemic stroke

Time Frame

Baseline to day 25

Title

Number of patients with non-CNS systemic embolism

Description

Ischemic stroke is defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by CNS infarction

Time Frame

Baseline to day 25

Title

Number of deaths

Description

Time Frame

Baseline to day 25

Title

Ventilation need

Description

Need for non-invasive or invasive ventilation

Time Frame

Baseline to day 25

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephan Windecker, Prof. Dr.

Organizational Affiliation

Bern University Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Jessa Ziekenhuis

City

Hasselt

ZIP/Postal Code

3500

Country

Belgium

Facility Name

ASST Rhodense

City

Garbagnate Milanese

ZIP/Postal Code

20024

Country

Italy

Facility Name

ASST Grande Ospedal Metropolitano Niguardia

City

Milan

ZIP/Postal Code

Country

Italy

Facility Name

Ospedale regionale Lugano

City

Lugano

State/Province

Ticino

ZIP/Postal Code

6900

Country

Switzerland

Facility Name

Bern University Hospital

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

31986264

Citation

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. Erratum In: Lancet. 2020 Jan 30;:

Results Reference

result

PubMed Identifier

32073213

Citation

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.

Results Reference

result

PubMed Identifier

32304646

Citation

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.

Results Reference

result

PubMed Identifier

32325026

Citation

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.

Results Reference

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PubMed Identifier

32302448

Citation

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.

Results Reference

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PubMed Identifier

32302438

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.

Results Reference

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PubMed Identifier

32330083

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.

Results Reference

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PubMed Identifier

34658014

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.

Results Reference

derived

Learn more about this trial

CorONa Virus edoxabaN ColchicinE (CONVINCE) COVID-19

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