Reducing Arrhythmia in Dialysis by Adjusting the Rx Electrolytes/Ultrafiltration, Study A (RADAR-A)

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

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.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Other: Potassium Removal Maximization; Other: Potassium Gradient Minimization; Other: Alkalosis Avoidance; Other: Acidosis avoidance; Diagnostic test: Point of Care Testing; Device: Cardiac Monitor

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Potassium Removal Maximization Strategy; 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; 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.; Diagnostic test: Point 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).; Other Names: BLUE I-STAT CHEM8+; Device: Cardiac 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.; Other Names: LINQ (Medtronic) Implantable Cardiac Loop Recorder (Carelink System)
Experimental: Potassium Gradient Minimization Strategy; 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; 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.; Diagnostic test: Point 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).; Other Names: BLUE I-STAT CHEM8+; Device: Cardiac 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.; Other Names: LINQ (Medtronic) Implantable Cardiac Loop Recorder (Carelink System)
Experimental: Alkalosis Avoidance Strategy; Dialysate bicarbonate concentration will be adjusted according to the results of point of care testing in order to prioritize avoiding alkalosis.	Other: Alkalosis 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.; Diagnostic test: Point 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).; Other Names: BLUE I-STAT CHEM8+; Device: Cardiac 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.; Other Names: LINQ (Medtronic) Implantable Cardiac Loop Recorder (Carelink System)
Experimental: Acidosis Avoidance Strategy; Dialysate bicarbonate concentration will be adjusted according to the results of point of care testing in order to prioritize avoiding acidosis.	Other: Acidosis 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 test: Point 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).; Other Names: BLUE I-STAT CHEM8+; Device: Cardiac 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.; Other Names: LINQ (Medtronic) Implantable Cardiac Loop Recorder (Carelink System)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of barriers to implementation	HD staff and patients will be surveyed once 3 subjects have completed 1 month of each trial and once 6 patients have completed each trial to identify barriers to implementation of the protocol.	2 years
Association of dialysis day, shift, and site with CSA	Exploratory analyses will assess association of dialysis day (Monday/Wednesday/Friday or Tuesday/Thursday/Saturday), shift (1st-3rd), and site with CSA.	2 years
Association of dialysis day, shift, and site with adherence	Exploratory analyses will assess association of dialysis day (Monday/Wednesday/Friday or Tuesday/Thursday/Saturday), shift (1st-3rd), and site with adherence.	2 years
Association of demographic and pre-randomization factors with adverse events	Exploratory analyses will assess age, sex, race, mean intra-dialytic weight gain, potassium concentration and HCO3 concentration in month prior to randomization on the incidence of adverse events.	2 years

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Duke University; National Institutes of Health (NIH)
• Investigators: Principal Investigator: David Charytan, MD, MSc, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2018
• Primary Completion (Actual): July 12, 2022
• Study Completion (Actual): October 14, 2022

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: April 26, 2018
• First Posted (Actual): May 9, 2018

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: hemodialysis; arrythmia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic; Arrhythmias, Cardiac
• Other Study ID Numbers: 18-01324; R34HL140477-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No