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

Apr 04, 2016
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Presenter/Author:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Ischemix LLC.
Date Presented:
04/04/2016
Date Published:
04/04/2016
Original Posted Date:
04/04/2016
References

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.

Keywords: ACC Annual Scientific Session, Acute Coronary Syndrome, Acute Kidney Injury, Coronary Angiography, Diabetes Mellitus, Exercise Test, Glomerular Filtration Rate, Heart Failure, Hypotension, Myocardial Infarction, Percutaneous Coronary Intervention, Renal Dialysis, Secondary Prevention, Thioctic Acid


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