Diana Lee, Mercer University College of Pharmacy 2015
Patiromer for Oral Suspension (FOS) is a nonabsorbed potassium binder in the pipeline for approval. Chronic kidney disease (CKD) patients frequently run into the problem of hyperkalemia due to the impairment of the kidneys to excrete potassium. Treatment guidelines recommend the use of RAAS inhibitors to preserve kidney function and delay progression to renal failure in CKD patients.1 However, RAAS inhibitors can cause or worsen hyperkalemia, posing an additional risk factor for hyperkalemia in this patient population. Patiromer may provide an alternate treatment option for hyperkalemia in patients with CKD.
|Title: Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors2|
|Design||Multi-center prospective trial with two phases:
Initial phase: Single-group, single-blindedWithdrawal phase: Placebo-controlled, single-blinded, randomized
|Objective||To assess the safety and efficacy of patiromer, a nonabsorbed potassium binder|
|Inclusion Criteria||18 to 80 years of age, had stage 3 or 4 chronic kidney disease (CKD), serum potassium levels of 5.1 to less than 6.5 mmol per liter (mmol/L) at two screenings, and had been receiving a stable dose of one or more renin-angiotensin-aldosterone system (RAAS) inhibitors for at least 28 days|
|Exclusion Criteria||Potassium-related electrocardiographic changes, severe gastrointestinal disorders, uncontrolled or unstable arrhythmias, recent cardiac surgery, kidney or heart transplantation, acute coronary syndrome, transient ischemic attack or stroke within the previous 2 months, and confirmed systolic blood pressure of 180 mm Hg or higher or less than 110 mm Hg or diastolic blood pressure of 110 mm Hg or higher or less than 60 mm Hg, type 1 diabetes, emergency treatment for type 2 diabetes or for exacerbation of acute heart failure within the previous 3 months, New York Heart Association class IV heart failure|
|Study Groups||Patients with chronic kidney disease (CKD) who were receiving RAAS inhibitors and had serum potassium levels of 5.1 to < 6.5 mmol/L were included in the initial treatment phase. In the withdrawal phase, eligible patients included those patients at week four with baseline potassium level of 5.5 to <6.5 mmol/L in whom level decreased to 3.8 to <5.1 mmol/L.|
|Methods||Initial treatment phase: Patients with mild hyperkalemia (5.1 to less than 5.5 mmol/L) received 4.2 g of patiromer twice daily. Patients with moderate-to-severe hyperkalemia received 8.4 g of patiromer twice daily. Randomized withdrawal phase: Eligible patients were randomly assigned in a 1:1 ratio to continue receiving patiromer or to receive placebo. Randomization was performed centrally and was stratified.
Serum potassium levels were measured at local and central laboratories at baseline and on day 3 of each phase and weekly thereafter.
|Duration||Four weeks (initial phase); eight weeks (withdrawal phase)|
|Primary Outcome Measure||Mean change in serum potassium level from baseline to week 4 (initial treatment phase); between-group difference in median change in the serum potassium level over the first 4 weeks of that second phase (withdrawal phase)|
|Statistical Analysis||Mean change in serum potassium levels and associated 95% confidence intervals (CI) were estimated with the use of a longitudinal repeated-measures model. In the randomized withdrawal phase, the estimated change in serum potassium levels between the two groups were based on ranks of observed changes.|
|Baseline Characteristics||Majority of the patients were white men with an average age of 64.2 (+/- 10.5) years. Forty-six percent had stage 3 CKD, approximately 45% had stage 4 CKD. A total of 97% had hypertension, 57% had type 2 diabetes, 42% had heart failure, and 25% had had a myocardial infarction. All patients were receiving at least one RAAS inhibitor at baseline. Non-RAAS-inhibitor diuretics were used in 54% of the patients.|
|Results||Initial treatment phase: Among 237 patients who received patiromer, the mean change in the serum potassium level was -1.01 +/- 0.03 mmol/L (95% CI, -1.07 to -0.95; P<0.001). At week 4, 76% (95% CI, 70 to 81) had reached the target potassium level (3.8 to <5.1 mmol per liter).
Randomized withdrawal phase: Subsequently, 107 patients were randomized to either patiromer (n=55) or placebo (n=52). The estimated median change in the potassium level during this second phase was 0.72 mmol/L in the placebo and 0 mmol/L in the patiromer group (95%CI, 0.46 to 0.99; P<0.001).
|Adverse Events||Common Adverse Events: Initial phase: mild to moderate constipation (11%), diarrhea (3%), hypomagnesesmia (3%), nausea (3%), anemia (3%), chronic renal failure (3%), hypokalemia (3%)|
|Serious Adverse Events:
Initial phase: 1% (none were fatal and unrelated to patiromer treatment)
|Percentage that Discontinued due to Adverse Events: 6% (initial phase); 2% (withdrawal phase)|
|Study Author Conclusions||In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia.|
According to this study, Patiromer seems to be a great option for CKD patients with hyperkalemia. Patiromer is efficacious in decreasing potassium levels with a low incidence of hypokalemia and other adverse effects. However, the trial did exhibit some shortcomings including the absence of blinding the researchers and participants, the absence of control for patient’s diet, and a short term in therapy.
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Mangement of Chronic Kidney Disease. Kidney inter., Suppl. 2013;3:1-150.
- Weir MR, Bakris GL, Bushinksy DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med 2015;372:211-221.