Clinical Potassium Pilot Study

In this pilot study, 30 prevalent hemodialysis patients will undergo three regular hemodialysis sessions during which various potassium assessments will be performed. Pre- (t1) and post-dialysis (t2) plasma potassium levels (K+Pl) will be measured using standard ion-selective electrodes. These values will be correlated to K+ determine in saliva probes (K+Sa) using genetically encoded potassium ion indicators (GEPIIs). Additionally, continuous ECG will be recorded during each hemodialysis treatment and potassium assessment (K+ECG) will be performed upon ECG-based parameters and correlated to K+Pl.

Study Overview

• Status: Completed
• Conditions: Hyperkalemia
• Intervention / Treatment: Device: GEPII; Device: Ion-selective electrodes

Detailed Description

Cardiovascular diseases are among the leading causes of death in industrialized countries. Medical therapy for these diseases has seen significant progress, much of which is based on agents interfering with the renin-angiotensin-aldosterone system (angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, mineralocorticoid receptor antagonists, neprilysin inhibitors). However, these agents bear the side effect of reducing renal potassium (K+) excretion and may thus lead to elevation of blood K+ Levels (hyperkalemia). Hyperkalemia is a potentially life-threatening condition, which in its most severe forms requires immediate medical attention, since there is imminent danger of dangerous arrhythmias and sudden cardiac death. Therefore, hyperkalemia is a leading reason to withdraw potentially lifesaving therapy in a significant number of patients, which is considered to have a negative impact on patient outcomes. Recently, novel intestinal potassium binders have been shown to be efficient in reducing incidence and severity of hyperkalemia These compounds have very recently been shown to allow extending the benefits of antihypertensive therapy with spironolactone to patients with chronic kidney disease with refractory hypertension . Yet due to preanalytical problems as well as time and cost-restraints, out-patient monitoring of serum or plasma potassium levels has proven problematic.

The plasma potassium level and kinetics at two timepoints before and after a hemodialysis session as determined by either standard of care (i.e. ion selective electrode) will be compared to the potassium level measured in (i) saliva (salivary potassium [K+Sa]) or (ii) determined based on electrocardiogram (K+ECG). Patients suffering from end-stage renal disease undergoing hemodialysis (HD) frequently present with severe hyperkalemia prior to a HD session. During HD treatment, K+ levels undergo unphysiologically rapid changes due to K+ removal via HD as well as due to changes in acid-base status. Thus, HD patients represent a unique population in whom significant K+ derangements and rapid K+ Level changes predictably occur and where these phenomena can be investigated in a safe environment.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 90 years of age
• End stage-renal disease or acute kidney injury patient undergoing hemodialysis
• Ability to provide oral and written informed consent
• Ability and willingness to comply with study procedures
• Willingness to not consume foods or drinks other than water during dialysis session

Exclusion Criteria:

• Intraventricular conduction abnormalities (left- or right bundle branch block, trifascicular block) which interfere with K+ECG determination
• Active inflammation or infection of the oral mucous membranes or dentition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: GEPII; All patients who completed the study.	Device: GEPII; Saliva probes (K+Sa) will be measured using genetically encoded potassium ion indicators (GEPIIs); Device: Ion-selective electrodes; Plasma potassium levels (K+Pl) will be measured using standard ion-selective electrodes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative difference in change of K+Sa at t2 versus t1	Assess the performance of K+Sa compared to K+Pl	Pre- (t1) and immediately post-dialysis (t2)
ECG P wave height	Comparison of the relative change of K+ECG at t2 versus t1	Pre- (t1) and immediately post-dialysis (t2)
ECG PR interval	Comparison of the relative change of K+ECG at t2 versus t1	Pre- (t1) and immediately post-dialysis (t2)
ECG QRS duration	Comparison of the relative change of K+ECG at t2 versus t1	Pre- (t1) and immediately post-dialysis (t2)
ECG maximum R wave height	Comparison of the relative change of K+ECG at t2 versus t1	Pre- (t1) and immediately post-dialysis (t2)
ECG QT interval	Comparison of the relative change of K+ECG at t2 versus t1	Pre- (t1) and immediately post-dialysis (t2)
ECG ST segment depression	Comparison of the relative change of K+ECG at t2 versus t1	Pre- (t1) and immediately post-dialysis (t2)
ECG maximum T wave height	Comparison of the relative change of K+ECG at t2 versus t1	Pre- (t1) and immediately post-dialysis (t2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of false positive measurements, i.e. percentage where severe hyperkalemia [K+>6.0 mmol/L] was detected by means of K+ECG, which was not present in K+Pl	Assess the performance of K+ECG compared to K+Pl	Pre- (t1) and immediately post-dialysis (t2)
Percentage of false negative measurement, i.e. percentage where severe hyperkalemia [K+>6.0 mmol/L] was not detected by means of K+ECG, which was present in K+Pl	Assess the performance of K+ECG compared to K+Pl	Pre- (t1) and immediately post-dialysis (t2)
Severe hyperkalemia [K+Pl ≥ 6.5 mmol/L] detection rate using K+ECG: comparison of automated detection using the K+ECG algorithm vs experienced electrophysiologist.	Assess the performance of K+ECG algorithm vs experienced electrophysiologist.	Pre- (t1) and immediately post-dialysis (t2)

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: NGFI Next Generation Fluorescence Imaging GmbH
• Investigators: Principal Investigator: Alexander H. Kirsch, MD, Medical University of Graz; Principal Investigator: Andras T. Deak, MD, Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2020
• Primary Completion (Actual): September 9, 2020
• Study Completion (Actual): September 9, 2020

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 15, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: hemodialysis; plasma potassium measurement; saliva potassium measurement; fluorescence assay; ECG-based potassium estimation; Förster resonance energy transfer
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia
• Other Study ID Numbers: CPPS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No