End Stage Renal Disease
Conditions
Keywords
arrythmia, hemodialysis
Brief summary
The primary purpose of this study is to test the feasibility of trials which change the dialysate (dialysis bath prescription) of potassium and bicarbonate according to a standardized algorithm and according to the results of blood testing performed prior to each dialysis. In addition, the trial will provide estimates of the extent to which performing dialysis in this way lowers the risk of abnormal heart rhythms in people with kidney failure who are being treated with chronic hemodialysis.
Detailed description
Within four weeks of consent, subjects will have an Implantable Loop Recorder (ILR) (Medtronic LINQ) device implanted. Subjects will be given a transmitter/charger and a Patient Care Assistant which they will be required to keep for the duration of their participation in the study. ILR tracings will be uploaded automatically and reviewed by the study team for the occurrence of clinically significant arrhythmia. Following ILR implantation, subjects will have 1 month of standard dialysis and will crossover in random order between four month-long periods of dialysis guided by the results of the point of care testing. Whole blood will be obtained by dialysis staff and immediately tested on a point of care chemistry analyzer according to the manufacturer's protocol prior to each dialysis session. The randomized intervention periods will include algorithms that alter the potassium bath in order to a) maximize potassium removal or b) minimize potassium removal as well as a second set of algorithms that alter the bicarbonate bath in order to c) limit acidosis or d) limit alkalosis.
Interventions
OTHERPotassium Removal Maximization
This intervention will test whether prioritizing lower potassium dialysate to reduce the incidence of hyperkalemia reduces the incidence of clinically significant arrhythmias compared to an approach minimizing intradialytic fall in serum potassium by using higher potassium dialysates to minimize serum-dialysate potassium gradients. This will be achieved by utilizing an algorithm which couples point-of-care-testing with the choice of one of two dialysate potassium concentrations (2 or 3 mEq/L) that are widely available in dialysis clinics.
OTHERPotassium Gradient Minimization
This intervention will test whether minimizing intradialytic fall in serum potassium by using higher potassium dialysates to minimize serum-dialysate potassium gradients reduces the incidence of clinically significant arrhythmias compared to an approach prioritizing lower potassium dialysate to reduce the incidence of hyperkalemia. This will be achieved by utilizing an algorithm which couples point-of-care-testing with the choice of one of two dialysate potassium concentrations (2 or 3 mEq/L) that are widely available in dialysis clinics.
OTHERAlkalosis Avoidance
The bicarbonate (HCO3) concentration will be adjusted according to the results of point of care testing of serum chemistries and an algorithm prioritizing alkalosis avoidance by use of lower dialysate HCO3 concentrations.
OTHERAcidosis avoidance
The bicarbonate (HCO3) concentration will be adjusted according to the results of point of care testing of serum chemistries and an algorithm prioritizing acidosis avoidance by use of higher dialysate HCO3 concentrations.
DIAGNOSTIC_TESTPoint of Care Testing
POC testing will use the Abbott BLUE I-STAT CHEM8+ , a portable, handheld device that provides lab quality analysis within 2-3 minutes using a few drops of whole blood (≤100uL).
DEVICECardiac Monitor
Device is one-third of the size of a triple-A battery and is placed subcutaneously in the left chest during a brief procedure that can be done in-office under local anesthesia.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Duke University
National Institutes of Health (NIH)
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Maintenance hemodialysis therapy for end-stage renal disease * Age 18-85 years (subjects between 18-40 years old will be required to have at least one of the following: history of congestive failure, diabetes, coronary or peripheral vascular disease, or arrhythmia) * \>30 days since dialysis initiation * Ability to provide informed consent
Exclusion criteria
* Expected survival \<6 monthsRenal transplant, transfer to home or peritoneal dialysis, or to non-study hemodialysis facility anticipated within 6 months * Prisoners or cognitive disability preventing informed consent * Pregnancy. A pregnancy test will be required for women of child bearing potential prior to enrollment. A pregnancy test will not be required for women past the age of child-bearing potential \>55 years old, women with a history of surgical sterilization, or for women \<55 years of age who have not had a menses within the past 12 months. * Skin condition, immune dysfunction, history of multiple infections or other condition which increases risk of local infection with ILR placement * Bleeding disorder or anti-coagulation that cannot be reversed for ILR placement * Existing pacemaker, implantable monitor or defibrillator which precludes device placement * Chronic, persistent AF. Defined as the presence of persistent AF on all available EKGs at time of recent screening. * Hemoglobin \<8 g/dL-Serum K \>6.5 or \<3.5 mEq/L within 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adherence With Proposed Interventions | Up to Week 24 | Adherence will be assessed as the percent of sessions in which POC testing is completed and the dialysate is adjusted according to the algorithm. |
| Number of Participants Enrolled Per Month | Up to Week 24 | Assessment of recruitment feasibility. |
| Proportion of Participants Who Experienced Potassium Intervention-Specific Complications | Up to Week 24 | Potassium Intervention-Specific Complications are defined as either severe potassium abnormalities (potassium ≥ 6.5 or ≤ 3.0 mEq/L) or unscheduled HD or hospitalization for hyper/hypokalemia in the absence of a missed treatment. |
| Proportion of Participants Who Experience Bicarbonate Intervention-Specific Complications | Up to Week 24 | Bicarbonate Intervention-Specific Complications are defined as severe HCO3 abnormalities (HCO3 \<20 or \>32 mEq/L) or unscheduled HD or hospitalization for acid base abnormalities in the absence of a missed treatment. |
| Mean Monthly Duration of Clinically Significant Arrhythmia (CSA) | Up to Week 24 | CSA will be defined on the basis of arrhythmias likely to lead to sudden cardiac arrest (SCA) or serious morbidity and mortality and will include AF, asystole ≥3 seconds, bradycardia ≤40 beats per minute lasting ≥6 seconds, and sustained VT ≥130 beats per minute lasting ≥30 seconds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality | Up to Week 24 | Number of participants who die due to any cause. |
| Percent of Sessions in Which POC-Guided Dialysate Prescription Differs From Standard of Care-Guided Prescription | Up to Week 24 | The impact of POC testing on trial design will be measured as the percent of sessions in which the POC-guided dialysate prescription differs from a hypothetical prescription in which the choice of dialysate is based solely on the once-monthly lab (usual care). |
| Cardiovascular Mortality | Up to Week 24 | Number of participants who die due to cardiovascular-related causes. |
| Mean Duration of Atrial Fibrillation | Up to Week 24 | — |
| Incidence of Potentially Lethal Arrhythmias | Up to Week 24 | Potentially lethal arrhythmias defined as asystole, sustained VT, bradycardia for ≥6 seconds. |
| Number of Screened Patients Who Are Enrolled | Up to Week 24 | Secondary feasibility measure to assess the size of the necessary screening pool. |
| Incidence of Hospitalization | Up to Week 24 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Sequence B1B2K1K2 Participants assigned to receive Alkalosis Avoidance Strategy, then Acidosis Avoidance Strategy, then Potassium Removal Maximization Strategy, then Potassium Gradient Minimization Strategy. | 5 |
| Intervention Sequence B2B1K2K1 Participants assigned to receive Acidosis Avoidance Strategy, then Alkalosis Avoidance Strategy, then Potassium Gradient Minimization Strategy, then Potassium Removal Maximization Strategy. | 4 |
| Intervention Sequence K1K2B1B2 Participants assigned to receive Potassium Removal Maximization Strategy, then Potassium Gradient Minimization Strategy, then Alkalosis Avoidance Strategy, then Acidosis Avoidance Strategy. | 4 |
| Intervention Sequence K2K1B2B1 Participants assigned to receive Potassium Gradient Minimization Strategy, then Potassium Removal Maximization Strategy, then Acidosis Avoidance Strategy, then Alkalosis Avoidance Strategy. | 6 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Interventional Crossover Period 1 | Death | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Intervention Sequence B1B2K1K2 | Total | Intervention Sequence K2K1B2B1 | Intervention Sequence K1K2B1B2 | Intervention Sequence B2B1K2K1 |
|---|---|---|---|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 13 | 59.9 years STANDARD_DEVIATION 11.655 | 54.0 years STANDARD_DEVIATION 11.9 | 64.0 years STANDARD_DEVIATION 12.8 | 59.7 years STANDARD_DEVIATION 8.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 15 Participants | 5 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 8 Participants | 4 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 7 Participants | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United States | 5 participants | 19 participants | 6 participants | 4 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 16 Participants | 5 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 17 | 0 / 16 | 1 / 16 | 2 / 17 |
| other Total, other adverse events | 4 / 17 | 3 / 16 | 1 / 16 | 3 / 17 |
| serious Total, serious adverse events | 3 / 17 | 3 / 16 | 3 / 16 | 5 / 17 |
Outcome results
Primary
Adherence With Proposed Interventions
Adherence will be assessed as the percent of sessions in which POC testing is completed and the dialysate is adjusted according to the algorithm.
Time frame: Up to Week 24
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Potassium Removal Maximization Strategy | Adherence With Proposed Interventions | 88 Percentage of sessions |
| Potassium Gradient Minimization Strategy | Adherence With Proposed Interventions | 90 Percentage of sessions |
| Alkalosis Avoidance Strategy | Adherence With Proposed Interventions | 83 Percentage of sessions |
| Acidosis Avoidance Strategy | Adherence With Proposed Interventions | 80 Percentage of sessions |
Primary
Mean Monthly Duration of Clinically Significant Arrhythmia (CSA)
CSA will be defined on the basis of arrhythmias likely to lead to sudden cardiac arrest (SCA) or serious morbidity and mortality and will include AF, asystole ≥3 seconds, bradycardia ≤40 beats per minute lasting ≥6 seconds, and sustained VT ≥130 beats per minute lasting ≥30 seconds.
Time frame: Up to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Removal Maximization Strategy | Mean Monthly Duration of Clinically Significant Arrhythmia (CSA) | 497 Seconds | Standard Deviation 817 |
| Potassium Gradient Minimization Strategy | Mean Monthly Duration of Clinically Significant Arrhythmia (CSA) | 60.8 Seconds | Standard Deviation 56 |
| Alkalosis Avoidance Strategy | Mean Monthly Duration of Clinically Significant Arrhythmia (CSA) | 1020 Seconds | Standard Deviation 2060 |
| Acidosis Avoidance Strategy | Mean Monthly Duration of Clinically Significant Arrhythmia (CSA) | 7950 Seconds | Standard Deviation 26000 |
Primary
Number of Participants Enrolled Per Month
Assessment of recruitment feasibility.
Time frame: Up to Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Potassium Removal Maximization Strategy | Number of Participants Enrolled Per Month | 0.7 Patients per month |
Primary
Proportion of Participants Who Experience Bicarbonate Intervention-Specific Complications
Bicarbonate Intervention-Specific Complications are defined as severe HCO3 abnormalities (HCO3 \<20 or \>32 mEq/L) or unscheduled HD or hospitalization for acid base abnormalities in the absence of a missed treatment.
Time frame: Up to Week 24
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Potassium Removal Maximization Strategy | Proportion of Participants Who Experience Bicarbonate Intervention-Specific Complications | 0.17 Proportion of participants |
| Potassium Gradient Minimization Strategy | Proportion of Participants Who Experience Bicarbonate Intervention-Specific Complications | 0.046 Proportion of participants |
Primary
Proportion of Participants Who Experienced Potassium Intervention-Specific Complications
Potassium Intervention-Specific Complications are defined as either severe potassium abnormalities (potassium ≥ 6.5 or ≤ 3.0 mEq/L) or unscheduled HD or hospitalization for hyper/hypokalemia in the absence of a missed treatment.
Time frame: Up to Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Potassium Removal Maximization Strategy | Proportion of Participants Who Experienced Potassium Intervention-Specific Complications | 0.0062 Proportion of participants |
| Potassium Gradient Minimization Strategy | Proportion of Participants Who Experienced Potassium Intervention-Specific Complications | 0 Proportion of participants |
Secondary
All-Cause Mortality
Number of participants who die due to any cause.
Time frame: Up to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Potassium Removal Maximization Strategy | All-Cause Mortality | 1 Participants |
| Potassium Gradient Minimization Strategy | All-Cause Mortality | 0 Participants |
| Alkalosis Avoidance Strategy | All-Cause Mortality | 1 Participants |
| Acidosis Avoidance Strategy | All-Cause Mortality | 2 Participants |
Secondary
Cardiovascular Mortality
Number of participants who die due to cardiovascular-related causes.
Time frame: Up to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Potassium Removal Maximization Strategy | Cardiovascular Mortality | 1 Participants |
| Potassium Gradient Minimization Strategy | Cardiovascular Mortality | 0 Participants |
| Alkalosis Avoidance Strategy | Cardiovascular Mortality | 0 Participants |
| Acidosis Avoidance Strategy | Cardiovascular Mortality | 1 Participants |
Secondary
Incidence of Hospitalization
Time frame: Up to Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Potassium Removal Maximization Strategy | Incidence of Hospitalization | 3 Number of Hospitalizations |
| Potassium Gradient Minimization Strategy | Incidence of Hospitalization | 4 Number of Hospitalizations |
| Alkalosis Avoidance Strategy | Incidence of Hospitalization | 2 Number of Hospitalizations |
| Acidosis Avoidance Strategy | Incidence of Hospitalization | 3 Number of Hospitalizations |
Secondary
Incidence of Potentially Lethal Arrhythmias
Potentially lethal arrhythmias defined as asystole, sustained VT, bradycardia for ≥6 seconds.
Time frame: Up to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Removal Maximization Strategy | Incidence of Potentially Lethal Arrhythmias | 2 Number of Potentially Lethal Arrhythmias | Standard Deviation 1.32 |
| Potassium Gradient Minimization Strategy | Incidence of Potentially Lethal Arrhythmias | 2 Number of Potentially Lethal Arrhythmias | Standard Deviation 1.32 |
| Alkalosis Avoidance Strategy | Incidence of Potentially Lethal Arrhythmias | 0 Number of Potentially Lethal Arrhythmias | Standard Deviation 0 |
| Acidosis Avoidance Strategy | Incidence of Potentially Lethal Arrhythmias | 3 Number of Potentially Lethal Arrhythmias | Standard Deviation 1.57 |
Secondary
Mean Duration of Atrial Fibrillation
Time frame: Up to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Removal Maximization Strategy | Mean Duration of Atrial Fibrillation | 1440 Seconds | Standard Deviation 0 |
| Potassium Gradient Minimization Strategy | Mean Duration of Atrial Fibrillation | 120 Seconds | Standard Deviation 0 |
| Alkalosis Avoidance Strategy | Mean Duration of Atrial Fibrillation | 1170 Seconds | Standard Deviation 2180 |
| Acidosis Avoidance Strategy | Mean Duration of Atrial Fibrillation | 189 Seconds | Standard Deviation 110 |
Secondary
Number of Screened Patients Who Are Enrolled
Secondary feasibility measure to assess the size of the necessary screening pool.
Time frame: Up to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Potassium Removal Maximization Strategy | Number of Screened Patients Who Are Enrolled | 19 Participants |
Secondary
Percent of Sessions in Which POC-Guided Dialysate Prescription Differs From Standard of Care-Guided Prescription
The impact of POC testing on trial design will be measured as the percent of sessions in which the POC-guided dialysate prescription differs from a hypothetical prescription in which the choice of dialysate is based solely on the once-monthly lab (usual care).
Time frame: Up to Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Potassium Removal Maximization Strategy | Percent of Sessions in Which POC-Guided Dialysate Prescription Differs From Standard of Care-Guided Prescription | 55.80 Percentage of sessions | Standard Deviation 49.1 |
| Potassium Gradient Minimization Strategy | Percent of Sessions in Which POC-Guided Dialysate Prescription Differs From Standard of Care-Guided Prescription | 41.20 Percentage of sessions | Standard Deviation 33.7 |
| Alkalosis Avoidance Strategy | Percent of Sessions in Which POC-Guided Dialysate Prescription Differs From Standard of Care-Guided Prescription | 90.20 Percentage of sessions | Standard Deviation 20.1 |
| Acidosis Avoidance Strategy | Percent of Sessions in Which POC-Guided Dialysate Prescription Differs From Standard of Care-Guided Prescription | 88.90 Percentage of sessions | Standard Deviation 26.2 |