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

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ClinicalTrials.gov Identifier: NCT03519347
Recruitment Status : Not yet recruiting
First Posted : May 9, 2018
Last Update Posted : May 15, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Duke University
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
David Charytan M.D., Brigham and Women's Hospital

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.

Condition or disease Intervention/treatment Phase
End Stage Renal Disease Other: Potassium Removal Maximization Other: Potassium Gradient Minimization Other: Alkalosis Avoidance Other: Acidosis avoidance Phase 2

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  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Reducing Arrhythmia in Dialysis by Adjusting the Rx Electrolytes/Ultrafiltration, Study 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
Estimated Study Start Date : July 1, 2018
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Potassium

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.

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.

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.

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.




Primary Outcome Measures :
  1. Adherence with Proposed Interventions [ Time Frame: 2 years ]
    Adherence will be assessed as the percent of sessions in which POC testing is completed and the dialysate is adjusted according to the algorithm.

  2. Recruitment feasibility [ Time Frame: 2 years ]
    Recruitment feasibility will be analyzed by testing whether an overall recruitment rate of 1 patient/month is achieved in each trial (1-sample test).

  3. Incidence of severe potassium abnormalities [ Time Frame: 6 months ]
    Severe potassium abnormalities are defined as potassium ≥6.5 or ≤3.0 mEq/L or unscheduled HD or hospitalization for hyper/hypokalemia in the absence of a missed treatment.

  4. Incidence of severe HCO3 abnormalities [ Time Frame: 6 months ]
    Severe HCO3 abnormalities are defined as HCO3 <20 or >32 mEq/L, or unscheduled HD or hospitalization for acid base abnormalities in the absence of a missed treatment.

  5. Change in duration of clinically significant arrhythmia (CSA) per month [ Time Frame: 6 months ]
    The total monthly duration of CSA (in minutes) will be utilized as the primary efficacy endpoint in comparing each pair of interventions (K removal maximization vs. minimization, acidosis vs. alkalosis avoidance, aggressive vs. conservative UF). In the event of incomplete follow-up, CSA duration will be indexed to follow-up time. 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. CSA's will be adjudicated by study electrophysiologists.


Secondary Outcome Measures :
  1. Comparison of pre- and post-correction adherence [ Time Frame: 2 years ]
    This measure will assess adherence to the protocol following any corrective measures made in response to surveys of dialysis staff.

  2. Accuracy of point of care (POC) testing [ Time Frame: 2 years ]
    POC electrolyte measurements will be compared with usual care monthly labs to assess accuracy of POC testing.

  3. Comparison of POC-guided dialysate prescription and standard-of-care dialysate prescription [ Time Frame: 2 years ]
    The impact of POC testing on trial design will be 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.

  4. Association of individual interventions with atrial fibrillation [ Time Frame: 6 months ]
    This measure will assess the effect of the interventions on the duration of atrial fibrillation.

  5. Association of individual interventions on potentially lethal arrhythmia [ Time Frame: 6 months ]
    This measure will assess the effect of the interventions on the duration of potentially lethal arrhythmias defined as asystole, sustained VT, bradycardia for ≥6 seconds.

  6. The occurrence of clinically significant arrhythmias requiring intervention [ Time Frame: 6 months ]
    This measure will assess the effect of the interventions on occurrence of arrhythmia requiring clinical intervention.

  7. All-cause mortality [ Time Frame: 2 years ]
  8. Cardiovascular mortality [ Time Frame: 2 years ]
  9. Hospitalization [ Time Frame: 2 years ]
  10. Proportion of screened patients enrolled [ Time Frame: 2 years ]
    The percent of screened patients enrolled will be calculated as a secondary feasibility measure to assess the size of the necessary screening pool. Reasons for non-enrollment (vis-à-vis inclusion and exclusion criteria and patient and physician preferences) will be assessed to determine the potential for protocol modification to improve recruitment.


Other Outcome Measures:
  1. Identification of barriers to implementation [ Time Frame: 2 years ]
    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. Association of dialysis day, shift, and site with CSA [ Time Frame: 2 years ]
    Exploratory analyses will assess association of dialysis day (Monday/Wednesday/Friday or Tuesday/Thursday/Saturday), shift (1st-3rd), and site with CSA.

  3. Association of dialysis day, shift, and site with adherence [ Time Frame: 2 years ]
    Exploratory analyses will assess association of dialysis day (Monday/Wednesday/Friday or Tuesday/Thursday/Saturday), shift (1st-3rd), and site with adherence.

  4. Association of demographic and pre-randomization factors with adverse events [ Time Frame: 2 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03519347


Contacts
Contact: David M Charytan, MD, MSc 617-525-7718 dcharytan@bwh.harvard.edu
Contact: Dan E Aurian-Blajeni, BSc, BSc 617-525-7814 daurian-blajeni@bwh.harvard.edu

Locations
United States, North Carolina
Duke University School of Medicine Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Patrick Pun, MD    919-672-2464    patrick.pun@duke.edu   
Sponsors and Collaborators
Brigham and Women's Hospital
National Institutes of Health (NIH)
Duke University
National Heart, Lung, and Blood Institute (NHLBI)

Responsible Party: David Charytan M.D., Associate Professor, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT03519347     History of Changes
Other Study ID Numbers: 2017P001737
R34HL140477-01 ( U.S. NIH Grant/Contract )
First Posted: May 9, 2018    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Dialysis Solutions
Pharmaceutical Solutions