Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether once-daily dosing of patiromer will reduce the frequency of hyperkalemic episodes in ESRD (end stage renal disease) study participants who receive conventional hemodialysis (HD). The study objective is to determine if patiromer administered orally once a day with breakfast or lunch will reduce episodes of hyperkalemia in ESRD study participants who receive thrice-weekly HD.

Detailed Description
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This is a prospective, randomized, open-label trial. Eligible ESRD patients who are on thrice weekly HD schedule will be screened from retrospective review of clinical and laboratory parameters from our clinical practice group. A total of 40 study participants (randomized 1:1 study drug: usual care) will be enrolled. Duration of study medication exposure will be 4 weeks. The total duration of study, from enrollment until the end of the washout period will be 7 weeks. This is a proof of concept study, to determine whether administration of patiromer has the potential to change the risk category for ESRD patients who are on conventional HD schedules. In addition, the study will develop and pilot study procedures that could be implemented in a large-scale clinical trial. By nature of the limited size of the study, the power of the trial will be limited. Reducing serum potassium with the use of low dialysate potassium is actually associated with an increased risk of sudden cardiac death. Furthermore, HD patients already carry a high pill burden, and it is unclear if prescription of an additional oral medication will reduce the frequency of episodic hyperkalemia.

Official Title
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Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients Treated With Hemodialysis (PEARL-HD)

Conditions
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Hyperkalemia, End Stage Renal Disease

Intervention / Treatment
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* Drug: Patiromer Oral Powder Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and Females, age at least 18 years ESRD treated with thrice-weekly HD for ≥ 6 months. At least two measured pre-dialysis serum [K] ≥ 5.5 mEq/L or one [K] ≥ 6.0 mEq/L noted over the past three months Current use of dialysate with potassium concentration ≤ 2 mEq/L Typical consumption of at least two meals per day Have received customary dietary instruction over prior month Considered by the treating physician(s) to be in otherwise stable clinical condition. If patient is of childbearing potential, he/she will be willing to avoid pregnancy during the study using an acceptable birth control method. Exclusion Criteria: Not considered by the treating physician(s) to be adherent with recommended dialysis schedule and prescribed medications Life expectancy < 3 months Dialysis-dependent for less than 6 months Non-elective hospitalization in prior 3 months Currently prescription of oral potassium supplements In the prior 3 months, therapy with oral potassium-lowering medication Underlying severe gastrointestinal disorders, including history of ischemic bowel. Corrected serum calcium concentration > 10.5 mg/dL in prior three months Anticipated kidney transplant within the next 3 months Prisoners or others who are involuntarily incarcerated or detained Pregnant, breastfeeding, or considering pregnancy. Participation in a clinical trial of an experimental treatment within the past 30 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective, randomized, open-label trial. Eligible ESRD patients who are on thrice weekly HD schedule will be screened from retrospective review of clinical and laboratory parameters from our clinical practice group. A total of 40 patients (randomized 1:1 study drug: usual care) will be enrolled. Duration of study medication exposure will be 4 weeks. The total duration of study, from enrollment until the end of the washout period will be 7 weeks.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patiromer Oral Powder Product<br>Patients randomized to the patiromer arm will initiate on 8.4 g/day (one pack) given once a day with breakfast or lunch (in place of the full dose of phosphate binder), to start at the end of Week 0. The patiromer dose will be titrated based on serum potassium concentrations drawn on HD1 of Weeks 1, 2, and 3. Patiromer will be increased by 8.4 g/day if K ≥ 5.1 meq/L, decreased by 8.4 g/day if K < 4.0 mEq/L, and patiromer will be discontinued if K < 3.5 mEq/L. | Drug: Patiromer Oral Powder Product<br>* Patients randomized to the patiromer arm will initiate on 8.4 g/day (one pack) given once a day with breakfast or lunch (in place of the full dose of phosphate binder), to start at the end of Week 0. The patiromer dose will be titrated based on serum potassium concentrations drawn on HD1 of Weeks 1, 2, and 3. Patiromer will be increased by 8.4 g/day if K ≥ 5.1 meq/L, decreased by 8.4 g/day if K < 4.0 mEq/L, and patiromer will be discontinued if K < 3.5 mEq/L. Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol<br>* Other names: Valtressa;|
| No Intervention: Usual care arm<br>Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of episodes of serum K ≥ 5.5 mEq/L | To determine if patiromer administered orally once a day with the mid-day meal will reduce episodes of hyperkalemia in ESRD patients who receive thrice-weekly HemoDiaylsis | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients with serum K > 5.5 mEq/L | To determine the between-group differences in percent of patients with serum K > 5.5 mEq/L | 4 weeks | 
| Average dose of patiromer that was given in treatment arm | To determine the efficacy and dosing of patiromer in ESRD patients. | 4 weeks | 
| Number of additional hemodialysis treatments due to hyperkalemia. | To determine the between-group differences in need for additional hemodialysis treatments due to hyperkalemia | 4 weeks | 
| Number of significant arrhythmia events as detected with cardiac monitors in Week 4. | To determine the between-group differences in pre-specified significant arrhythmia events as detected with cardiac monitors in Week 4. | 4 weeks | 
| Difference percentage in serum albumin concentrations. | To determine the between-group differences in serum albumin concentrations. | 4 weeks | 
| Difference percentage in PTH concentrations. | To determine the between-group differences in PTH concentrations. | 4 weeks | 
| Number of patients who completed all study visits. | To determine feasibility of a large-scale hemodialysis-based trial. | 4 weeks | 
| Change percentage in serum potassium concentration two weeks after study drug is discontinued. | To determine the change in serum potassium concentration two weeks after study drug is discontinued | 6 weeks | 
| Change percentage in serum phosphorus concentration two weeks after study drug has been discontinued. | To determine the change in serum phosphorus concentration two weeks after study drug has been discontinued | 6 weeks | 
| Number of > 1000 PVC/24 hours. | Presence of > 1000 PVC/24 hours | 4 weeks | 
| Number of significant arrhythmias. | The between-group and Week-0-to-Week-4-differences in significant arrhythmias will be evaluated. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis