Safety and Efficacy of CMX-2043 for Periprocedural Injury Protection in Subjects Undergoing Coronary Angiography at Risk of Radio-contrast Induced Nephropathy - CARIN

Description:

The goal of the trial was to compare the safety and efficacy of CMX-2043 in reducing acute kidney injury (AKI) following percutaneous coronary intervention (PCI).

Contribution to the Literature: The CARIN study suggests that CMX-2043 at three different doses was not more efficacious than placebo in reducing AKI following coronary angiography/PCI.



Study Design

Patients undergoing coronary angiography were randomized in a 1:1:1:1 fashion to CMX-2043 2.4 mg/kg (n = 87), 3.6 mg/kg (n = 94), 4.8 mg/kg (n = 87), or placebo (n = 93).

  • Total number of enrollees: 3,503
  • Duration of follow-up: 90 days
  • Mean patient age: 67 years
  • Percentage female: 42%

Other salient features/characteristics:

  • Baseline estimated glomerular filtration rate (eGFR) 45 ml/min/1.73 m2
  • Hydration therapy: 45%

Inclusion criteria:

  • Coronary angiography with high probability of PCI
  • Either acute coronary syndrome (excluding ST-elevation myocardial infarction [STEMI]), planned PCI with >75 ml of contrast, or≥2 abnormal ischemic regions by stress test
  • Either eGFR 15.0-45.0 ml/min or eGFR  45.1-60.0 ml/min and at least one of the following:
    • >75 years of age
    • Diabetes mellitus
    • Ejection fraction <40%
    • Hypotension
    • Congestive heart failure

Exclusion criteria:

  • End-stage renal disease (eGFR <15)
  • STEMI
  • Cardiac arrest
  • Life-threatening arrhythmia

Principal Findings:

Primary outcome, AKI at 4 days, for CMX-2043 2.4 mg/kg vs 3.6 mg/kg vs 4.8 mg/kg vs. placebo: 25.6% vs. 25.3% vs. 18.9% vs. 18.6%, p > 0.05

Secondary outcomes:

  • Mean eGFR at 90 days: 42.7 vs. 45.8 vs. 43.8 vs. 44.6, p > 0.05
  • Major adverse kidney events: 48.2% vs. 55.6% vs. 46.3% vs. 38.2%, p > 0.05
  • Dialysis: 1.2% vs. 1.1% vs. 0% vs. 1.1%, p > 0.05
  • Major adverse cardiac events: 2.4% vs. 11.1% vs. 3.8% vs. 4.5%, p > 0.05
  • MI: 1.2% vs. 7.8% vs. 1.3% vs. 1.1%, p > 0.05

Interpretation:

The results of this trial indicate that CMX-2043 at three different doses was not more efficacious than placebo in reducing AKI following coronary angiography/PCI. There were also no differences in periprocedural MI or other cardiovascular outcomes. CMX-2043 is a potent version of alpha-lipoic acid and is thought to have salutary effects on kidney tissue by multiple mechanisms.

References:

Presented by Dr. Deepak L. Bhatt at the American College of Cardiology Annual Scientific Session, Chicago, IL, April 4, 2016.


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