AMETHYST–Diabetic Nephropathy - AMETHYST-DN

Sep 16, 2015
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Relypsa
Date Published:
07/14/2015
Original Posted Date:
09/16/2015
References

Description:

The goal of the trial was to evaluate treatment with the potassium-binding polymer, patiromir, in diabetic subjects with chronic kidney disease and hyperkalemia, on an angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB).

Contribution to the Literature: The phase 2 AMETHYST-DN trial showed that patiromir reduced serum potassium levels in diabetics with chronic kidney disease.

Study Design

  • Randomized
  • Parallel
  • Stratified

Diabetic subjects with hyperkalemia were divided into stratum 1 (serum potassium 5.0-5.5 mEq/L) or stratum 2 (serum potassium >5.5 to <6.0 mEq/L).

In stratum 1, subjects were randomized to patiromir 8.4 g/day (n = 74), patiromir 16.8 g/day (n = 74), or patiromir 25.2 g/day (n = 74). In stratum 2, subjects were randomized to patiromir 16.8 g/day (n = 26), patiromir 25.2 g/day (n = 28), or patiromir 33.6 g/day (n = 30).

Inclusion criteria:

  • Diabetes and chronic kidney disease (estimated glomerular filtration rate 15-60 cc/min/1.73 m2)
  • Serum potassium >5.0 mEq/L
  • Receiving an ACE inhibitor or ARB
  • Total number of enrollees: 306
  • Duration of follow-up: 52 weeks
  • Mean patient age: 67 years
  • Percentage female: 39%
  • Percentage diabetics: 100%

Principal Findings:

The primary efficacy outcome, change in serum potassium at 4 weeks:

- Stratum 1: 0.35 for patiromir 8.4 g/day, 0.51 for patiromir 16.8 g/day, and 0.55 for patiromir 25.2 g/day

- Stratum 2: 0.87 for patiromir 16.8 g/day, 0.97 for patiromir 25.2 g/day, and 0.92 patiromir 33.6 g/day

Serum potassium reductions were sustained at 52 weeks.

The secondary outcome included worsening of chronic kidney disease at 52 weeks:

- Stratum 1: 6.8% for patiromir 8.4 g/day, 8.2% for patiromir 16.8 g/day, and 4.1% for patiromir 25.2 g/day

- Stratum 2: 11.5% for patiromir 16.8 g/day, 14.3% for patiromir 25.2 g/day, and 23.3% patiromir 33.6 g/day

Interpretation:

Among diabetics with chronic kidney disease and hyperkalemia, all doses of patiromir decreased serum potassium at 4 weeks, which was maintained at 52 weeks. The frequency of adverse events appeared favorable. This study will be used to inform the design of a phase 3 study.

References:

Bakris GL, Pitt B, Weir MR, et al., on behalf of the AMETHYST-DN Investigators. Effect of patiromir on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN randomized clinical trial. JAMA 2015;314:151-61.

Keywords: Angiotensin-Converting Enzyme Inhibitors, Diabetes Mellitus, Diabetic Nephropathies, Hyperkalemia, Kidney Failure, Chronic, Metabolic Syndrome, Potassium, Primary Prevention, Renal Insufficiency, Chronic


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