PEARL HF: RLY5016 reduceert serum kalium bij HF patiënten met CKD

Nieuws - 29 aug. 2010

PEARL HF: RLY5016 reduces serum potassium in HF patients with CKD

29 August 2010

Results from the phase IIb PEARL HF study show that treatment with RLY5016 leads to significant reductions in serum potassium and hyperkalemia for patients with heart failure (HF) and chronic kidney disease (CKD).

The researchers randomly assigned 104 patients to take the potassium-binding polymer RLY5016 30 g/day or placebo, in addition to 25 mg of spironolactone (titrated to 50 mg at 2 weeks), for 4 weeks to assess its influence on serum potassium level and the incidence of hyperkalemia (defined in this study as a serum potassium level of ≥5.5 mEq/L). RLY5016 produced a significant reduction both in the concentration of serum potassium from baseline and in the incidence of hyperkalemia. In addition, compared with controls, a significantly higher percentage of RLY5016-treated patients had their spironolactone dose titrated successfully.

  RLY5016 30 g/day (n=55) Placebo (n=49) p-value
Primary endpoint
Change in serum K from baseline (mEq/L)



Secondary endpoint
Incidence of hyperkalemia (%)



Spironolactone increased (%) 91 74 0.019

“Currently the risk of hyperkalemia has limited the use of…renin-angiotensin-aldosterone system inhibitors, which exposes patients to further cardiac risk. These trial data are therefore very significant,” concluded lead investigator Bertram Pitt (University of Michigan School of Medicine, USA).

Study details
The Parallel Evaluation of RLY5016 in HF (PEARL-HF) investigators recruited a total of 104 patients aged an average of 68.3 years old. All the patients had HF and CKD grade 3 or 4. They had a baseline serum potassium concentration of between 4.3 and 5.1 mEq/L and were taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta blockers, or had a documented history of hyperkalemia leading to discontinuation of a HF therapy.

The primary endpoint of a significant reduction in serum potassium level at 28 days in the treatment versus the placebo group was successfully reached, with a significant between-group difference of -0.45 mEq/L (p<0.001).

The secondary endpoints of a significant decrease in the incidence of hyperkalemia and increase in the number of patients who successfully had their spironolactone levels raised were also achieved.

Pitt noted that the drug seemed to be most effective in patients with more severe renal failure (eGFR <45 ml/min) and in whom there were no cases of hyperkalemia, compared with 7% and 7% in those with moderate (eGFR <60 ml/min) and mild (eGFR >60 ml/min) renal failure, respectively.

No serious drug-related adverse events were reported, although 4% of both groups had a serious non-study-related adverse event. Withdrawal due to medication side-effects was low, at 7% versus 6% in the placebo group. In total, 54% of the treatment and 31% of the placebo group reported at least one adverse event, generally mild and gastrointestinal.

Around 6% of patients developed hypokalemia (potassium level of <3.5 mEq/L), but Pitt and colleagues said that reducing the dose of RLY5016 to 20 g/day could solve this problem, and they have plans to test this theory.

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