Clinical Trial Results:
Efficacy and Safety of Edoxaban and or Colchicine for patients with SARS-CoV-2 infection managed in the out of hospital setting (COVID 19)
Summary
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EudraCT number |
2020-002234-32 |
Trial protocol |
BE IT |
Global end of trial date |
31 Aug 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Sep 2023
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First version publication date |
10 Sep 2023
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Other versions |
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Summary report(s) |
CONVINCE-CIP CONVINCE SAP CONVINCE Synopsis Final Report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CONVINCE
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04516941 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Insel Gruppe AG
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Sponsor organisation address |
Fraiburgstrase 18, Bern, Switzerland,
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Public contact |
Prof.Stephan Windecker, Insel Gruppe AG - Inselspital Universitätsklinik für Kardiologie, +41 316325000, kardio.studien@insel.ch
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Scientific contact |
Prof.Stephan Windecker, Insel Gruppe AG - Inselspital Universitätsklinik für Kardiologie, +41 316325000, kardio.studien@insel.ch
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Jun 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Aug 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Aug 2022
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
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
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Protection of trial subjects |
- Regular patient follow-up with adverse event collection
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Apr 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 26
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Country: Number of subjects enrolled |
Italy: 5
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Country: Number of subjects enrolled |
Switzerland: 29
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Worldwide total number of subjects |
60
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EEA total number of subjects |
31
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
58
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients ≥ 18 years old with symptoms compatible with active Coronavirus infection and laboratory confirmed SARS-CoV-2 infection (under RT PCR) who are managed at home or in another out-of-hospital setting | |||||||||||||||
Pre-assignment
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Screening details |
Eligible patients can be consented and randomised at any within 7 days from first SARS- CoV-2 positive diagnosis | |||||||||||||||
Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
No
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Arm title
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Edoxaban only | |||||||||||||||
Arm description |
SARS-CoV-2 positive patients managed outside the hospital. Edoxaban 60 mg q.d., or 30 mg q.d. in patients with CrCl = or <50 ml/min or body weight equal, less than 60 kg and concomitant prescription of ciclosporin, dronedarone, erythromycin, ketoconazole, from randomization to end of study visit at day 25 (+/-3). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Lixiana (Edoxaban)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Edoxaban 60 mg q.d., or 30 mg q.d. in patients with CrCl = or <50 ml/min or body weight equal, less than 60 kg and concomitant prescription of ciclosporin, dronedarone, erythromycin,
ketoconazole, from randomization to end of study visit at day 25 (+/-3).
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Arm title
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No Edoxaban | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Colchicine only | |||||||||||||||
Arm description |
Colchicine at 0.5 mg per os (PO) twice daily for the first 3 days and then once daily from randomization to study visit FU at day 14 (+/-3) days. Treatment could be continued to the day 25 (+3/-3 days). If the creatinine clearance (CrCl) was between 15-30 ml/min the loading dosage was 0.5 mg once daily while the maintenance dosage remained unchanged. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Colchicine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Colchicine at 0.5 mg per os (PO) twice daily for the first 3 days and then once daily from randomization to study visit FU at day 14 (+/-3) days. Treatment could be continued to the day 25
(+3/-3 days). If the creatinine clearance (CrCl) was between 15-30 ml/min the loading dosage was 0.5 mg once daily while the maintenance dosage remained unchanged.
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Arm title
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No Colchicine | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups [1]
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Reporting group title |
Edoxaban only
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Reporting group description |
SARS-CoV-2 positive patients managed outside the hospital. Edoxaban 60 mg q.d., or 30 mg q.d. in patients with CrCl = or <50 ml/min or body weight equal, less than 60 kg and concomitant prescription of ciclosporin, dronedarone, erythromycin, ketoconazole, from randomization to end of study visit at day 25 (+/-3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
No Edoxaban
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Colchicine only
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Reporting group description |
Colchicine at 0.5 mg per os (PO) twice daily for the first 3 days and then once daily from randomization to study visit FU at day 14 (+/-3) days. Treatment could be continued to the day 25 (+3/-3 days). If the creatinine clearance (CrCl) was between 15-30 ml/min the loading dosage was 0.5 mg once daily while the maintenance dosage remained unchanged. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
No Colchicine
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same. Justification: 60 patients were consented; 1 of those refused further participation in the study, 59 of those were randomized: 16 in Edoxaban + Colchicine group, 13 in Edoxaban group, 14 in Colchicine group, 16 in standard of care (this means 29 in Edoxaban group, 30 in No Edoxaban group, 30 in Colchicine group, 29 in No Colchicine group). All 59 patients completed the study. |
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End points reporting groups
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Reporting group title |
Edoxaban only
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Reporting group description |
SARS-CoV-2 positive patients managed outside the hospital. Edoxaban 60 mg q.d., or 30 mg q.d. in patients with CrCl = or <50 ml/min or body weight equal, less than 60 kg and concomitant prescription of ciclosporin, dronedarone, erythromycin, ketoconazole, from randomization to end of study visit at day 25 (+/-3). | ||
Reporting group title |
No Edoxaban
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Reporting group description |
- | ||
Reporting group title |
Colchicine only
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Reporting group description |
Colchicine at 0.5 mg per os (PO) twice daily for the first 3 days and then once daily from randomization to study visit FU at day 14 (+/-3) days. Treatment could be continued to the day 25 (+3/-3 days). If the creatinine clearance (CrCl) was between 15-30 ml/min the loading dosage was 0.5 mg once daily while the maintenance dosage remained unchanged. | ||
Reporting group title |
No Colchicine
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Reporting group description |
- |
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End point title |
Edoxaban vs. no active treatment [1] | |||||||||||||||
End point description |
This study has 2 co-primary endpoint
Edoxaban vs. no active treatment
Major vascular thrombotic events (MVTE) at 25 (+/-3) days defined as a composite 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
• Death
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End point type |
Primary
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End point timeframe |
Major vascular thrombotic events (MVTE) at 25 (+/-3) days
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Among COVID-19 patients managed in the out-of-hospital setting, this study showed no difference in the two co-primary endpoints with edoxaban and/or colchicine versus standard of care. In consideration of the premature trial discontinuation and the consequent insufficient study power, the current study does not allow to draw definitive conclusions on the safety and the efficacy of edoxaban and/or colchicine administration in SARS-CoV-2 infected patients managed outside the hospital. |
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No statistical analyses for this end point |
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End point title |
Colchicine vs no active treatment [2] | |||||||||||||||
End point description |
This study has 2 co-primary endpoints, one each randomization as follows
Colchicine vs no active treatment
The SARS-CoV-2 detection rates at day 14 (+/-3) under RT PCR or freedom from death or
hospitalisation
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End point type |
Primary
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End point timeframe |
The SARS-CoV-2 detection rates at day 14 (+/-3) under RT PCR or freedom from death or
hospitalisation
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Among COVID-19 patients managed in the out-of-hospital setting, this study showed no difference in the two co-primary endpoints with edoxaban and/or colchicine versus standard of care. In consideration of the premature trial discontinuation and the consequent insufficient study power, the current study does not allow to draw definitive conclusions on the safety and the efficacy of edoxaban and/or colchicine administration in SARS-CoV-2 infected patients managed outside the hospital. |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Enrolment to End of Study (25 days +/-3 days post randomization)
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
25
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Frequency threshold for reporting non-serious adverse events: 0.1% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Among COVID-19 patients managed in the out-of-hospital setting, this study showed no difference in the two co-primary endpoints with edoxaban and/or colchicine versus standard of care. In consideration of the premature trial discontinuation and the consequent insufficient study power, the current study does not allow to draw definitive conclusions on the safety and the efficacy of edoxaban and/or colchicine administration in SARS-CoV-2 infected patients managed outside the hospital. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |