Canakinumab in COVID-19 Cardiac Injury - Three C Study

Nov 13, 2020
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Novartis
Date Presented:
11/13/2020
Original Posted Date:
11/13/2020
References

Contribution To Literature:

Among hospitalized patients with COVID-19 and evidence of cardiac injury and higher inflammation, canakinumab did not significantly improve outcomes with either 600 mg or 300 mg dose compared with placebo.

Description:

The goal of the trial was to assess the safety and efficacy of canakinumab among hospitalized patients with coronavirus disease 2019 (COVID-19).

Study Design

This was a phase II trial. Patients were randomized in a 1:1:1 fashion to either intravenous canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). Usual care was provided at the discretion of the clinicians.

  • Total number of enrollees: 45
  • Duration of follow-up: 28 days
  • Mean patient age: 68.8 years
  • Percentage female: 27%
  • African-American: 38%

Inclusion criteria:

  • Hospitalized for COVID-19, with documented upper respiratory tract specimen positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA
  • High-sensitivity troponin T >99th upper reference limit
  • N-terminal pro-B-type natriuretic peptide greater than the age-adjusted upper reference limit
  • C-reactive protein >5 mg/dl

Other salient features/characteristics:

  • Need for invasive ventilation: 22.2%
  • Other therapies: corticosteroids: 47%, remdesivir: 47%
  • Mean left ventricular ejection fraction: 60%

Principal Findings:

The primary outcome was time to clinical improvement at 14 days. The recovery rate ratio for canakinumab 600 mg vs. placebo was 1.2 (95% confidence interval [CI] 0.47-3.03, p = 0.47), and for canakinumab 300 mg vs. placebo, was 0.60 (95% CI 0.22-1.62, p = 0.3).

Secondary outcomes:

  • Recovery rate ratio for canakinumab 600 mg vs. placebo at 28 days: 2.15 (95% CI 0.91-5.11, p = 0.12)
  • Clinical improvement for canakinumab 600 mg vs. canakinumab 300 mg vs. placebo: 93.3% vs. 78.6% vs. 68.8% (p = 0.09)
  • Any serious event for canakinumab 600 mg vs. canakinumab 300 mg vs. placebo: 33.3% vs. 42.9% vs. 43.8%

Interpretation:

The results of this phase II pilot trial indicate that among hospitalized patients with COVID-19 and evidence of cardiac injury and higher inflammation, canakinumab did not significantly improve outcomes with either 600 mg or 300 mg dose compared with placebo. This was a small trial and underpowered for seeing smaller differences.

Canakinumab is an 1L-1β inhibitor, that showed a beneficial impact on CRP and major adverse cardiac events in patients with a prior myocardial infarction.

References:

Presented by Dr. Paul C. Cremer at the American Heart Association Virtual Scientific Sessions, November 13, 2020.

Clinical Topics: COVID-19 Hub, Prevention, Novel Agents, Vascular Medicine

Keywords: AHA20, AHA Annual Scientific Sessions, Antibodies, Monoclonal, Coronavirus, COVID-19, C-Reactive Protein, Inflammation, Natriuretic Peptide, Brain, Primary Prevention, Respiration, Artificial, severe acute respiratory syndrome coronavirus 2, Stroke Volume, Troponin T


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