Clinical trial NCT03781089: Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients
Official title: Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients Treated With Hemodialysis (PEARL-HD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hyperkalemia
End Stage Renal Disease
Keywords: Hemodialysis
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Vifor Pharma
First posted: 2018-12-19
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Total Number of Episodes of Serum Potassium ≥ 5.5 mEq/L
timeFrame: Week 4
Secondary outcomes:
measure: Number of Episodes of Serum Potassium ≥ 5.5 mEq/L Per Participant
timeFrame: 4 weeks
measure: Median Daily Dose of Patiromer That Was Given in Treatment Arm
timeFrame: Week 3
measure: Number of Additional Hemodialysis Treatments Due to Hyperkalemia
timeFrame: 4 weeks
measure: Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline
timeFrame: Baseline
measure: Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4
timeFrame: Week 4
measure: Number of Participants Who Completed All Study Visits
timeFrame: 4 weeks
measure: Number of Participants With More Than 1000 Premature Ventricular Contractions (PVCs) in 24 Hours
timeFrame: 4 weeks
measure: Change in Serum Albumin Concentration
timeFrame: 4 weeks
measure: Change in Parathyroid Hormone (PTH) Concentration
timeFrame: 4 weeks
measure: Change in Serum Potassium Concentration Two Weeks After Study Drug is Discontinued
timeFrame: 6 weeks
measure: Change in Serum Phosphorus Concentration Two Weeks After Study Drug Has Been Discontinued
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: DaVita Dialysis Sites
state: North Carolina
Study officials:
affiliation: Duke University
name: John P Middleton, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.