End Stage Renal Disease, Hyperkalemia
Conditions
Keywords
Hemodialysis
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.
Interventions
DRUGPatiromer Oral Powder Product
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
Sponsors
Vifor Pharma
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
The study is open-label and therefore the subjects, coordinators and investigators are not blinded to the intervention. Titration of the patiromer will require viewing of the serum potassium values. During the data analysis, however, personnel involved will remain blinded.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Episodes of Serum Potassium ≥ 5.5 mEq/L | Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Daily Dose of Patiromer That Was Given in Treatment Arm | Week 3 | — |
| Number of Additional Hemodialysis Treatments Due to Hyperkalemia | 4 weeks | To determine the between-group differences in need for additional hemodialysis treatments due to hyperkalemia |
| Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Baseline | Clinically significant cardiac arrhythmias included sustained ventricular tachycardia (VT), ventricular fibrillation, asystolic cardiac arrest, non-sustained VT (≥ 3 beats but \< 30 seconds), \> 3 second pause), atrial fibrillation (\> 30 seconds), premature ventricular contractions \> 500/24h or bradycardia (heart rate \< 40 for 5 consecutive beats). |
| Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Week 4 | Clinically significant cardiac arrhythmias included sustained ventricular tachycardia (VT), ventricular fibrillation, asystolic cardiac arrest, non-sustained VT (≥ 3 beats but \< 30 seconds), \> 3 second pause), atrial fibrillation (\> 30 seconds), premature ventricular contractions \> 500/24h or bradycardia (heart rate \< 40 for 5 consecutive beats). |
| Number of Participants Who Completed All Study Visits | 4 weeks | To determine feasibility of a large-scale hemodialysis-based trial. |
| Number of Episodes of Serum Potassium ≥ 5.5 mEq/L Per Participant | 4 weeks | 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. |
| Change in Serum Albumin Concentration | 4 weeks | To determine the between-group differences in serum albumin concentrations. |
| Change in Parathyroid Hormone (PTH) Concentration | 4 weeks | To determine the between-group differences in PTH concentrations. |
| Change in Serum Potassium Concentration Two Weeks After Study Drug is Discontinued | 6 weeks | To determine the change in serum potassium concentration two weeks after study drug is discontinued |
| Change in Serum Phosphorus Concentration Two Weeks After Study Drug Has Been Discontinued | 6 weeks | To determine the change in serum phosphorus concentration two weeks after study drug has been discontinued |
| Number of Participants With More Than 1000 Premature Ventricular Contractions (PVCs) in 24 Hours | 4 weeks | PVCs are irregular contractions that start in the ventricles instead of the atria. |
Countries
United States
Participant flow
Recruitment details
Potential participants were identified from a population of individuals who had ESKD and were maintained on thrice-weekly hemodialysis at five outpatient clinics.
Pre-assignment details
A total of 36 individuals with ESKD were enrolled, and prior to randomization three were withdrawn (one due to severe hyperkalemia, one due to prolonged hospitalization, and one due to failure to obtain a baseline electrocardiogram).
Participants by arm
| Arm | Count |
|---|---|
| Patiromer Oral Powder Product 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.
Patiromer Oral Powder Product: 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 | 17 |
| Usual Care Arm Patients randomized to the usual care arm will undergo monitoring with laboratory measurements as outlined in the study protocol | 16 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Constipation | 1 | 0 |
| Overall Study | Positive pregnancy test | 0 | 1 |
Baseline characteristics
| Characteristic | Usual Care Arm | Total | Patiromer Oral Powder Product |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 11.1 | 56.2 years STANDARD_DEVIATION 11 | 54.1 years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 30 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 27 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 6 Participants | 4 Participants |
| Region of Enrollment United States | 16 Participants | 33 Participants | 17 Participants |
| Sex: Female, Male Female | 10 Participants | 15 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 18 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 16 |
| other Total, other adverse events | 5 / 17 | 5 / 16 |
| serious Total, serious adverse events | 2 / 17 | 2 / 16 |
Outcome results
Primary
Total Number of Episodes of Serum Potassium ≥ 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.
Time frame: Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patiromer Oral Powder Product | Total Number of Episodes of Serum Potassium ≥ 5.5 mEq/L | 13 episodes |
| Usual Care Arm | Total Number of Episodes of Serum Potassium ≥ 5.5 mEq/L | 41 episodes |
p-value: 0.024Wilcoxon (Mann-Whitney)
Secondary
Change in Parathyroid Hormone (PTH) Concentration
To determine the between-group differences in PTH concentrations.
Time frame: 4 weeks
Population: Data not collected due to limited resources.
Secondary
Change in Serum Albumin Concentration
To determine the between-group differences in serum albumin concentrations.
Time frame: 4 weeks
Population: Data not collected due to limited resources.
Secondary
Change 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
Time frame: 6 weeks
Population: Data not collected due to limited resources.
Secondary
Change 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
Time frame: 6 weeks
Population: Data not collected due to limited resources.
Secondary
Median Daily Dose of Patiromer That Was Given in Treatment Arm
Time frame: Week 3
Population: Not applicable to the Usual Care arm.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Patiromer Oral Powder Product | Median Daily Dose of Patiromer That Was Given in Treatment Arm | 8.4 grams/day | Standard Deviation 0 |
Secondary
Number of Additional Hemodialysis Treatments Due to Hyperkalemia
To determine the between-group differences in need for additional hemodialysis treatments due to hyperkalemia
Time frame: 4 weeks
Population: Data not collected. Post-dialysis serum potassium concentration was not measured, therefore unable to determine whether post-treatment hyperkalemia occurred.
Secondary
Number of Episodes of Serum Potassium ≥ 5.5 mEq/L Per Participant
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.
Time frame: 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patiromer Oral Powder Product | Number of Episodes of Serum Potassium ≥ 5.5 mEq/L Per Participant | 0 episodes per participant |
| Usual Care Arm | Number of Episodes of Serum Potassium ≥ 5.5 mEq/L Per Participant | 3 episodes per participant |
p-value: 0.024Wilcoxon (Mann-Whitney)
Secondary
Number of Participants Who Completed All Study Visits
To determine feasibility of a large-scale hemodialysis-based trial.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patiromer Oral Powder Product | Number of Participants Who Completed All Study Visits | 16 Participants |
| Usual Care Arm | Number of Participants Who Completed All Study Visits | 15 Participants |
Secondary
Number of Participants With More Than 1000 Premature Ventricular Contractions (PVCs) in 24 Hours
PVCs are irregular contractions that start in the ventricles instead of the atria.
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patiromer Oral Powder Product | Number of Participants With More Than 1000 Premature Ventricular Contractions (PVCs) in 24 Hours | 2 Participants |
| Usual Care Arm | Number of Participants With More Than 1000 Premature Ventricular Contractions (PVCs) in 24 Hours | 4 Participants |
Secondary
Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline
Clinically significant cardiac arrhythmias included sustained ventricular tachycardia (VT), ventricular fibrillation, asystolic cardiac arrest, non-sustained VT (≥ 3 beats but \< 30 seconds), \> 3 second pause), atrial fibrillation (\> 30 seconds), premature ventricular contractions \> 500/24h or bradycardia (heart rate \< 40 for 5 consecutive beats).
Time frame: Baseline
Population: One participant in Usual Care arm lost the cardiac monitor for week 4.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patiromer Oral Powder Product | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Premature ventricular contractions | 4 Participants |
| Patiromer Oral Powder Product | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Non-sustained VT events | 2 Participants |
| Patiromer Oral Powder Product | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Atrial fibrillation | 2 Participants |
| Patiromer Oral Powder Product | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Bradycardia events | 0 Participants |
| Usual Care Arm | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Bradycardia events | 0 Participants |
| Usual Care Arm | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Premature ventricular contractions | 2 Participants |
| Usual Care Arm | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Atrial fibrillation | 2 Participants |
| Usual Care Arm | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Baseline | Non-sustained VT events | 2 Participants |
Secondary
Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4
Clinically significant cardiac arrhythmias included sustained ventricular tachycardia (VT), ventricular fibrillation, asystolic cardiac arrest, non-sustained VT (≥ 3 beats but \< 30 seconds), \> 3 second pause), atrial fibrillation (\> 30 seconds), premature ventricular contractions \> 500/24h or bradycardia (heart rate \< 40 for 5 consecutive beats).
Time frame: Week 4
Population: One participant in Usual Care arm lost the cardiac monitor for week 4.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patiromer Oral Powder Product | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Atrial fibrillation | 2 Participants |
| Patiromer Oral Powder Product | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Premature ventricular contractions | 2 Participants |
| Patiromer Oral Powder Product | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Non-sustained VT events | 3 Participants |
| Patiromer Oral Powder Product | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Bradycardia events | 0 Participants |
| Usual Care Arm | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Bradycardia events | 1 Participants |
| Usual Care Arm | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Atrial fibrillation | 1 Participants |
| Usual Care Arm | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Non-sustained VT events | 2 Participants |
| Usual Care Arm | Number of Participants With Significant Arrhythmia Events as Detected With Cardiac Monitors at Week 4 | Premature ventricular contractions | 4 Participants |