Hyperkalemia
Conditions
Brief summary
This study assesses serum potassium and cardiac rhythm trends in subjects with end stage renal disease (ESRD) who are on 3 times weekly maintenance hemodialysis for at least 60 days. Dialysate K (relative potassium concentration in dialysate) must be stable for 2 weeks prior to enrollment.The number of subjects on 3K or higher dialysate will be limited to 60, with the remainder of the subjects on 1K or 2K dialysate.
Detailed description
This study assesses serum potassium and cardiac rhythm trends in subjects with end stage renal disease (ESRD) who are on 3 times weekly maintenance hemodialysis for at least 60 days. Approximately 240 Subjects who meet the eligibility criteria and sign the informed consent form can be enrolled in the study, after which a subject number will be assigned. The number of subjects on 3K or higher dialysate will be limited to 60, with the remainder of the subjects on 1K or 2K dialysate. Baseline data will be collected including subject demographics, dialysis prescription, and symptom assessment. In addition, results of clinical laboratory tests and urea reduction ratio (URR), dialyzer clearance-time-volume of distribution of urea (Kt/V), and intact parathyroid hormone (PTH) obtained within the 4 weeks prior to the first dialysis treatment on Study Day 1 will be collected from regular monthly labs to establish baseline. Subjects will be assessed in the dialysis clinic/research center over a period of 12 days. Subjects will start the study on the first day of a given week's dialysis regimen (ie, Monday or Tuesday). Subjects who are on a Monday, Wednesday, and Friday dialysis schedule will skip the Saturday visit, and subjects who are on a Tuesday, Thursday, and Saturday dialysis schedule will skip the Sunday visit during the 12-day study duration. Subjects will undergo blood collection at each visit, including 6 dialysis days and 5 inter-dialysis days. On dialysis days, blood samples will be collected immediately before and at the end of dialysis treatment. During the dialysis treatments on Study Days 1 and 3 only, additional blood samples will be obtained at 30 minutes and 1 hour (± 15 minutes) after the start of dialysis for chemistry. On inter-dialysis days, the dialysis clinic/research center will make an effort to collect blood samples at the same approximate time that dialysis treatment would have started on days of dialysis. Otherwise, samples may be collected when the subject is able to visit the dialysis clinic/research center. Vital signs including heart rate and blood pressure, and body weight will be collected at each visit. On dialysis days, both pre- and post-dialysis weights will be collected, along with vital signs obtained during dialysis. A specifically designed symptom assessment will also be performed at specified times throughout the study. The subjects will also undergo cardiac rhythm monitoring using a non-invasive, Food and Drug Administration cleared, wearable device (BodyGuardian® remote monitoring system) throughout the 12 days of participation in the study. This will be used to assess for cardiac arrhythmias, as well as to correlate S-K levels with signal-averaged, processed ECG.
Interventions
DEVICECardiac rhythm remote monitoring system
Non-invasive wearable remote cardiac rhythm monitoring system used throughout 12 days of study.
Sponsors
ZS Pharma, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent. * 18 years of age or older. * Subject has ESRD and has been stable and compliant (as determined by the investigator) on 3 times weekly maintenance hemodialysis for at least 60 days; the number of subjects on 3K or higher dialysate will be limited to 60, with the remainder of the subjects on 1K or 2K dialysate. Dialysate K must be stable for 2 weeks prior to enrollment. * Hemoglobin \> 9 g/dL. * Able to undergo peripheral venous sticks for blood draws on inter-dialysis days, or the dialysis/research team is able to use the dialysis access for blood draws on those days. * Subject or subject's caregiver at home can read and understand English and has the ability to use the BodyGuardian remote monitoring system.
Exclusion criteria
* Pregnancy. Sexually active women of child-bearing potential must have a negative pregnancy test before starting the study on Study Day 1. Women who are surgically sterile or those who are postmenopausal for at least 2 years are not considered to be a childbearing potential. * Subjects or bed partners with implanted pacemakers or defibrillators. * Known skin allergies or sensitivities to acrylic, hydrogel or silicone adhesives. * Fragile skin. * Participation in another clinical trial which may impact the results of this study. * Subjects who, in the opinion of investigator, are unable to perform the tasks associated with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Pre-dialysis HK After the LIDP in <3K Dialysate Patients | 12 Days | Incidence of pre-dialysis hyperkalemia (HK) in patients after the long inter-dialytic period (LIDP) in patients on \<3K dialysate. Hyperkalemia defined as serum potassium (S-K) \>5.0 mEq/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Pre-dialysis Hyperkalemia (HK) After the Long Inter-dialytic Period (LIDP) in Patients on ≥3K Dialysate. | 12 days | Incidence of pre-dialysis hyperkalemia (HK) in patients after the long inter-dialytic period (LIDP) in patients on ≥3K dialysate. Hyperkalemia defined as serum potassium (S-K) \>5.0 mEq/L. |
| Incidence of Cardiac Arrhythmias | 12 days | Incidence of serious cardiac arrhythmias in patients during the observational period. Serious arrhythmias defined as ventricular tachycardia or \> 5 sec pause. |
Countries
United States
Participant flow
Recruitment details
Patients with end stage renal disease on maintenance hemodialysis took part in the study at 17 sites in the United States.
Pre-assignment details
Cardiac rhythm was monitored using a 24-hour non-invasive, wearable device (BodyGuardian® remote monitoring system) throughout the study to assess for cardiac arrhythmias was to be worn by patients. One site did not perform cardiac rhythm monitoring.
Participants by arm
| Arm | Count |
|---|---|
| <3 K Dialysate Patients Patients on \<3 K dialysate and received all 6 hemodialysis treatments over 12 days. | 179 |
| ≥3K Dialysate Patients Patients on ≥3K dialysate who received all 6 hemodialysis treatments over 12 days | 33 |
| Total | 212 |
Baseline characteristics
| Characteristic | <3 K Dialysate Patients | ≥3K Dialysate Patients | Total |
|---|---|---|---|
| Age, Customized | 56.9 Years STANDARD_DEVIATION 12.4 | 58.5 Years STANDARD_DEVIATION 12.4 | 57.1 Years STANDARD_DEVIATION 12.5 |
| Sex/Gender, Customized Female | 64 Participants | 13 Participants | 77 Participants |
| Sex/Gender, Customized Male | 115 Participants | 20 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Incidence of Pre-dialysis HK After the LIDP in <3K Dialysate Patients
Incidence of pre-dialysis hyperkalemia (HK) in patients after the long inter-dialytic period (LIDP) in patients on \<3K dialysate. Hyperkalemia defined as serum potassium (S-K) \>5.0 mEq/L.
Time frame: 12 Days
Population: Per Protocol Population: all enrolled subjects who receive 6 dialysis treatments within the 12-day study period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| <3 K Dialysate Patients | Incidence of Pre-dialysis HK After the LIDP in <3K Dialysate Patients | Any pre-dialysis HK after LIDP, % | 50 Percent of participants |
| <3 K Dialysate Patients | Incidence of Pre-dialysis HK After the LIDP in <3K Dialysate Patients | Pre-dialysis HK after LIDP ( based on mean S-K), % | 37 Percent of participants |
Secondary
Incidence of Cardiac Arrhythmias
Incidence of serious cardiac arrhythmias in patients during the observational period. Serious arrhythmias defined as ventricular tachycardia or \> 5 sec pause.
Time frame: 12 days
Population: Patients who received all 6 hemodialysis treatments and wore Body Guardian Device, a non-invasive wearable remote cardiac rhythm monitoring system
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| <3 K Dialysate Patients | Incidence of Cardiac Arrhythmias | Atrial fibrillation | 51 % of patients |
| <3 K Dialysate Patients | Incidence of Cardiac Arrhythmias | Serious arrhythmias | 16 % of patients |
Secondary
Incidence of Pre-dialysis Hyperkalemia (HK) After the Long Inter-dialytic Period (LIDP) in Patients on ≥3K Dialysate.
Incidence of pre-dialysis hyperkalemia (HK) in patients after the long inter-dialytic period (LIDP) in patients on ≥3K dialysate. Hyperkalemia defined as serum potassium (S-K) \>5.0 mEq/L.
Time frame: 12 days
Population: Per protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| <3 K Dialysate Patients | Incidence of Pre-dialysis Hyperkalemia (HK) After the Long Inter-dialytic Period (LIDP) in Patients on ≥3K Dialysate. | Any pre-dialysis HK after LIDP, % | 36 % of patients |
| <3 K Dialysate Patients | Incidence of Pre-dialysis Hyperkalemia (HK) After the Long Inter-dialytic Period (LIDP) in Patients on ≥3K Dialysate. | Pre-dialysis HK after LIDP ( based on mean S-K), % | 21 % of patients |