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Canakinumab in Patients With COVID-19 and Type 2 Diabetes (CanCovDia)

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ClinicalTrials.gov Identifier: NCT04510493
Recruitment Status : Completed
First Posted : August 12, 2020
Last Update Posted : September 8, 2021
Sponsor:
Collaborators:
Novartis
Swiss National Science Foundation
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE August 11, 2020
First Posted Date  ICMJE August 12, 2020
Last Update Posted Date September 8, 2021
Actual Study Start Date  ICMJE October 23, 2020
Actual Primary Completion Date August 17, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2020)
unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint) [ Time Frame: within 4 weeks after treatment with canakinumab or placebo ]
Treatment and placebo will be compared on the basis of the unmatched win-ratio approach of Pocock. When comparing two patients, the winner will be determined by the first component in which the two patients differ (4 weeks after randomization):
  1. longer survival time
  2. longer ventilation-free time
  3. longer ICU-free time
  4. shorter hospitalization time
If there is no difference between treatment and Placebo: the win ratio is 1. If there is a difference between treatment and Placebo: the win ratio is not 1.
Original Primary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
unmatched win ratio after treatment with canakinumab compared to placebo [ Time Frame: within 4 weeks after treatment with canakinumab or placebo ]
unmatched win ratio determined by the ordered components:
  1. longer survival time
  2. longer ventilation-free time
  3. longer ICU-free time
  4. shorter hospitalization time
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
  • Time to clinical improvement [ Time Frame: From randomization up to 4 weeks ]
    Time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever comes first. "The seven-category ordinal scale consists of the following categories:
    1. not hospitalized with resumption of normal activities;
    2. not hospitalized, but unable to resume normal activities;
    3. hospitalized, not requiring supplemental oxygen;
    4. hospitalized, requiring supplemental oxygen;
    5. hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both;
    6. hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and
    7. death"
  • Death rate [ Time Frame: 4 weeks ]
    Death rate during the 4-week period after study treatment
  • Admission to intensive care unit (ICU) [ Time Frame: 4 weeks ]
    Admission to the intensive care unit from the medical ward during the 4-week period after study treatment
  • Secondary worsening of disease [ Time Frame: 4 weeks ]
    Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)
  • Prolonged hospital stay [ Time Frame: >3 weeks ]
    Prolonged hospital stay > 3 weeks
  • Change in ratio to baseline in the glycated hemoglobin [ Time Frame: Baseline, Day 29 and Day 90 ]
    Ratio to baseline in the glycated hemoglobin
  • Change in ratio to baseline in the fasting glucose [ Time Frame: Baseline, Day 29 ]
    Ratio to baseline in the fasting glucose
  • Change in ratio to baseline in the fasting insulin [ Time Frame: Baseline, Day 29 ]
    Ratio to baseline in the fasting insulin
  • Change in ratio to baseline in the fasting c-peptide [ Time Frame: Baseline, Day 29 ]
    Ratio to baseline in the fasting c-peptide
  • Ratio to baseline in the C-reactive protein (CRP) [ Time Frame: Baseline, Day 29 and Day 90 ]
    Ratio to baseline in the C-reactive protein (CRP)
  • Change in ratio to baseline in the D-dimer [ Time Frame: Baseline, Day 29 ]
    Ratio to baseline in the D-dimer
  • Change in ratio to baseline in the Natriuretic peptide (NTproBNP) [ Time Frame: Baseline, Day 29 and Day 90 ]
    Ratio to baseline in the Natriuretic peptide (NTproBNP)
  • Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR) [ Time Frame: Baseline, Day 29 and Day 90 ]
    Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)
  • Type of antidiabetic treatment at Day 29 [ Time Frame: Day 29 ]
    Type of antidiabetic treatment at Day 29
  • Number of antidiabetic treatment at Day 29 [ Time Frame: Day 29 ]
    Number of antidiabetic treatment at Day 29
  • Type of antidiabetic treatment at three months [ Time Frame: Month 3 ]
    Type of antidiabetic treatment at three months
  • Number of antidiabetic treatment at three months [ Time Frame: Month 3 ]
    Number of antidiabetic treatment at three months
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Canakinumab in Patients With COVID-19 and Type 2 Diabetes
Official Title  ICMJE Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial
Brief Summary The purpose of this study is to evaluate whether Canakinumab has beneficial effects on patients with Type 2 diabetes mellitus and coronavirus disease 19 (COVID19).
Detailed Description Patients with a metabolic syndrome (overweight, diabetes, hypertension) have a particularly bad outcome if infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). This may be explained by an over-activation of the Interleukin-1 (IL-1) beta system. Metabolic stress (increased glucose and lipid levels) induces NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) -mediated IL-1beta secretion. SARS-CoV2 also activates NLRP3. Therefore, the study proposes that metabolic stress in patients with overweight and diabetes potentiates COVID-19 induced hyperinflammatory syndrome leading to excess mortality in these vulnerable patients. Canakinumab (Ilaris®) is a recombinant, human monoclonal antibody antagonizing IL-1beta by blocking IL-1beta activity. The aim of the study is to investigate the effect of canakinumab in type 2 diabetic patients with COVID-19.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronavirus Infection
  • Diabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: Canakinumab
    Body weight adjusted dose in 250 ml 5% dextrose solution i.v. over 2 hours
    Other Name: Ilaris®
  • Drug: Placebo
    Aqua ad injectabilia in 250 ml 5% dextrose solution i.v. over 2 hours
    Other Name: Aqua ad injectabilia in 250 ml 5% dextrose solution
Study Arms  ICMJE
  • Active Comparator: active treatment arm
    Treatment with Canakinumab i.v. administered over 2 hours
    Intervention: Drug: Canakinumab
  • Placebo Comparator: placebo treatment arm
    placebo treatment
    Intervention: Drug: Placebo
Publications * Hepprich M, Mudry JM, Gregoriano C, Jornayvaz FR, Carballo S, Wojtusciszyn A, Bart PA, Chiche JD, Fischli S, Baumgartner T, Cavelti-Weder C, Braun DL, Gunthard HF, Beuschlein F, Conen A, West E, Isenring E, Zechmann S, Bucklar G, Aubry Y, Dey L, Muller B, Hunziker P, Schutz P, Cattaneo M, Donath MY. Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial. EClinicalMedicine. 2022 Sep 17;53:101649. doi: 10.1016/j.eclinm.2022.101649. eCollection 2022 Nov.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 17, 2020)
116
Original Estimated Enrollment  ICMJE
 (submitted: August 11, 2020)
112
Actual Study Completion Date  ICMJE August 17, 2021
Actual Primary Completion Date August 17, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of type 2 diabetes mellitus
  • Body mass index > 25 kg/m² (overweight)
  • Hospitalized with COVID-19

Exclusion Criteria:

  • Suspected or known untreated active bacterial, fungal, viral, or parasitic infection with the exception of COVID-19
  • Treatment with immunomodulators or immunosuppressant drugs, including but not limited to tocilizumab, tumor necrosis factor (TNF) inhibitors and anti-IL-17 agents within 5 half-lives or 30 days (whichever is longer) prior to randomization with the exception of anakinra which is excluded within 5 half-lives only. Note: Immunomodulators (topical or inhaled) for asthma and atopic dermatitis, and corticosteroids (any route of administration) such as dexamethasone are permitted.
  • History of hypersensitivity to canakinumab or to biologic drugs
  • Neutrophil count <1000/mm3
  • Pregnant or nursing (lactating) women
  • Participation in another study with investigational drug within the 30 days preceding and during the present study-
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04510493
Other Study ID Numbers  ICMJE 2020-02008; me20Donath2
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University Hospital, Basel, Switzerland
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Novartis
  • Swiss National Science Foundation
Investigators  ICMJE
Principal Investigator: Marc Donath, MD, Prof. University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism
PRS Account University Hospital, Basel, Switzerland
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP