Clinical Potassium Pilot Study

• ClinicalTrials.gov Identifier: NCT04251468
• Recruitment Status: Completed
• First Posted: February 5, 2020
• Last Update Posted: September 16, 2020
• Sponsor: Medical University of Graz
• Collaborator: NGFI Next Generation Fluorescence Imaging GmbH
• Information provided by (Responsible Party): Medical University of Graz

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hyperkalemia	Device: GEPII; Device: Ion-selective electrodes	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Clinical Potassium Pilot Study
• Actual Study Start Date: April 29, 2020
• Actual Primary Completion Date: September 9, 2020
• Actual Study Completion Date: September 9, 2020

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. Relative difference in change of K+Sa at t2 versus t1 [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Assess the performance of K+Sa compared to K+Pl
2. ECG P wave height [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Comparison of the relative change of K+ECG at t2 versus t1
3. ECG PR interval [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Comparison of the relative change of K+ECG at t2 versus t1
4. ECG QRS duration [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Comparison of the relative change of K+ECG at t2 versus t1
5. ECG maximum R wave height [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Comparison of the relative change of K+ECG at t2 versus t1
6. ECG QT interval [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Comparison of the relative change of K+ECG at t2 versus t1
7. ECG ST segment depression [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Comparison of the relative change of K+ECG at t2 versus t1
8. ECG maximum T wave height [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Comparison of the relative change of K+ECG at t2 versus t1

Secondary Outcome Measures :

1. 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 [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Assess the performance of K+ECG compared to K+Pl
2. 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 [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Assess the performance of K+ECG compared to K+Pl
3. 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. [ Time Frame: Pre- (t1) and immediately post-dialysis (t2) ]
   Assess the performance of K+ECG algorithm vs experienced electrophysiologist.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Austria

Medical University of Graz

Graz, Austria

Sponsors and Collaborators

Medical University of Graz

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

More Information

• Responsible Party: Medical University of Graz
• ClinicalTrials.gov Identifier: NCT04251468
• Other Study ID Numbers: CPPS
• First Posted: February 5, 2020
• Last Update Posted: September 16, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medical University of Graz:

plasma potassium measurement; saliva potassium measurement; hemodialysis; fluorescence assay; ECG-based potassium estimation; Förster resonance energy transfer

Additional relevant MeSH terms:

Hyperkalemia; Water-Electrolyte Imbalance; Metabolic Diseases