Reducing Arrhythmia in Dialysis by Adjusting the Rx Electrolytes/Ultrafiltration, Study A

Study Overview
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Brief Summary
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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
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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.

Official Title
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Radar-A: A Phase 2 Multi-center Study to Evaluate the Safety and Tolerability of Using Point-of-Care-Guided Manipulation of Dialysate Potassium and Dialysate Bicarbonate to Prevent Hemodialysis-Associated Arrhythmias

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Other: Potassium Removal Maximization
* Other: Potassium Gradient Minimization
* Other: Alkalosis Avoidance
* Other: Acidosis avoidance
* Diagnostic Test: Point of Care Testing
* Device: Cardiac Monitor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Potassium Removal Maximization Strategy<br>Dialysate potassium will be adjusted according to the results of point of care testing in order to maximize potassium removal and avoid hyperkalemia. | Other: Potassium Removal Maximization<br>* 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.<br>Diagnostic Test: Point of Care Testing<br>* 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).<br>* Other names: BLUE I-STAT CHEM8+;Device: Cardiac Monitor<br>* 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.<br>* Other names: LINQ (Medtronic) Implantable Cardiac Loop Recorder (Carelink System);|
| Experimental: Potassium Gradient Minimization Strategy<br>Dialysate potassium will be adjusted according to the results of point of care testing in order to minimize the flux of potassium. | Other: Potassium Gradient Minimization<br>* 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.<br>Diagnostic Test: Point of Care Testing<br>* 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).<br>* Other names: BLUE I-STAT CHEM8+;Device: Cardiac Monitor<br>* 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.<br>* Other names: LINQ (Medtronic) Implantable Cardiac Loop Recorder (Carelink System);|
| Experimental: Alkalosis Avoidance Strategy<br>Dialysate bicarbonate concentration will be adjusted according to the results of point of care testing in order to prioritize avoiding alkalosis. | Other: Alkalosis Avoidance<br>* 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.<br>Diagnostic Test: Point of Care Testing<br>* 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).<br>* Other names: BLUE I-STAT CHEM8+;Device: Cardiac Monitor<br>* 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.<br>* Other names: LINQ (Medtronic) Implantable Cardiac Loop Recorder (Carelink System);|
| Experimental: Acidosis Avoidance Strategy<br>Dialysate bicarbonate concentration will be adjusted according to the results of point of care testing in order to prioritize avoiding acidosis. | Other: Acidosis avoidance<br>* 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.<br>Diagnostic Test: Point of Care Testing<br>* 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).<br>* Other names: BLUE I-STAT CHEM8+;Device: Cardiac Monitor<br>* 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.<br>* Other names: LINQ (Medtronic) Implantable Cardiac Loop Recorder (Carelink System);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Week 24 | 
| Number of Participants Enrolled Per Month | Assessment of recruitment feasibility. | Up to Week 24 | 
| 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. | Up to Week 24 | 
| 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. | Up to Week 24 | 
| 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. | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Up to Week 24 | 
| Mean Duration of Atrial Fibrillation |  | Up to Week 24 | 
| Incidence of Potentially Lethal Arrhythmias | Potentially lethal arrhythmias defined as asystole, sustained VT, bradycardia for ≥6 seconds. | Up to Week 24 | 
| Number of Screened Patients Who Are Enrolled | Secondary feasibility measure to assess the size of the necessary screening pool. | Up to Week 24 | 
| Incidence of Hospitalization |  | Up to Week 24 | 
| All-Cause Mortality | Number of participants who die due to any cause. | Up to Week 24 | 
| Cardiovascular Mortality | Number of participants who die due to cardiovascular-related causes. | Up to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arrythmia, hemodialysis