Targeted Potassium Levels for Prevention of ICD Therapy

Arrhythmia Prevention in High Risk Cardiovascular Patients Using Targeted Potassium Levels

This study evaluates whether a rigorously controlled high-normal level of serum-potassium (4.5-5.0 mEq/L) using dietary recommendations, potassium supplements and mineralocorticoid receptor antagonists will results in a lower incidence of cardiac arrhythmias in patients with an ICD. Patients will be randomized to this treatment or a control arm, where patients will receive usual guideline recommended follow-up.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Ventricular Tachycardia; Implantable Defibrillator User; Hypokalemia; Ventricular Arrhythmias and Cardiac Arrest; Hyperkalemia
• Intervention / Treatment: Combination product: Targeted serum potassium level

Detailed Description

There is solid evidence that potassium-sparing drugs increase survival and ameliorates symptoms in heart failure patients and post-hoc studies have suggested that high-normal levels of blood potassium levels (p-K) markedly decreases the risk of malignant arrhythmias in cardiovascular patients.

This trial will randomize patients implanted with implantable cardioverter defibrillators (ICDs), who remain at high risk of life-threatening cardiac arrhythmias, to a standard therapy or standard therapy plus a regimen to keep high-normal p-K levels. The study will enroll 1,000 patients from the outpatient pacemaker clinics at Rigshospitalet and Gentofte hospital. Using a planned regime to increase p-K using inexpensive drugs and potassium supplements, the patients enrolled and followed with regular controls as well as continuous monitoring using existing home monitoring systems over a period of 4 years for the primary endpoint of appropriate ICD therapy and all cause mortality. Including analysis, the trial will be running for 5 years

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Christian Joens, MD, PhD; Phone Number: +1-647-562-6151; Email: Christian.joens.02@regionh.dk
• Study Contact Backup: Name: Niels Risum, MD, PhD; Phone Number: +4523456073; Email: niels.risum.01@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Christian Joens, MD; Phone Number: +4535459863; Email: christian.joens.02@regionh.dk
    • Contact: Henning Bundgaard, Professor; Phone Number: +35450512; Email: henning.bundgaard@regionh.dk
    • Sub-Investigator: Niels Risum, MD
    • Sub-Investigator: Ulrik Winsloew, MD
  • Hellerup
    • Gentofte, Hellerup, Denmark, 2900
      • Recruiting
      • Gentofte University Hospital
      • Contact: Tommi B Lindhart, MD, PhD; Phone Number: 38672276; Email: tommi.bo.lindhart@regionh.dk
      • Contact: Kasper K Iversen, MD, DMSc; Phone Number: +4538686009; Email: Kasper.karmark.iversen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Implantable cardioverter defibrillator (ICD) or cardiac resynchronization pacemaker with ICD (CRT-D).
• Age >18 years

Exclusion Criteria:

• Estimated glomerular filtration rate (eGFR) <30 ml/h
• Pregnancy
• Lack of ability to understand and sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; ICD recipients in optimal Medical treatment as per guidelines according to their comorbidity
Experimental: Targeted serum potassium levels; ICD recipients recipients in optimal Medical treatment as per guidelines according to their comorbidity. In addition to guideline recommended treatment, this cohort will be treated to increase serum potassium levels to 4.5-5.0 mEq/L.	Combination product: Targeted serum potassium level; In the following order, following advices end prescriptions will be provided: 1) Potassium rich dietary advice, 2) Potassium supplementation, 3) mineralocorticoid receptor antagonists,

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first major event defined as a combination of: - first occurence of ECG documented ventricular tachycardia > 125 bpm lasting > 30 seconds - first occurence of any appropriate ICD therapy as documented by the ICD - All cause mortality	The time period with regards to the Time-to-Event Outcome Measures starts with the randomization of the patient. ECG documented tachycardia from ECGs or ICD interrogations will be obtained from hospitalizations or outpatients clinic visits via electronic records after patient consent. Information of ventricular tachyarrhythmia therapy will be obtained from home monitoring systems or interrogation of the ICD devices during in-clinic visits. Mortality will be obtained from danish electronic hospital files or the danish death registry.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first incidence of supraventricular arrhythmias as documented by ECG or the ICD	Any supraventricular tahcycardia documented on ECG, telemetry or as monitored/treated event on the ICD	4 years
Proportion of patients experiencing <92 % CRT-pacing for > 2 weeks (only CRT-D patients)	CRT-D home monitoring systems allow temporal evaluation of percentage of CRT pacing.	4 years
Time to first hospitalization for heart failure	Hospitalization with symptoms of heart failure and with a diagnosis of heart failure where treatment with i.v. diuretics was initiated.	4 years
Time to first hospitalization for cardiac arrhythmias	Hospitalization were records indicate that supraventricular or ventricular arrhythmias were implicated in the cause of the hospitalization	4 years
Time to hospitalization for electrolyte disturbances or kidney failure		4 years
First occurrence of appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation irrespective of outcome.	Ventricular tachy-arrhythmia therapy, which will be obtained from home monitoring systems or interrogation of the ICD devices during in-clinic visits. All ICD therapy is routinely adjudicated as appropriate or in-appropriate by electrophysiologists at the study sites.	4 years
Time to first occurence of inappropriate ICD therapy	Any cause of inappropriate shock including atrial fibrillation, other supraventricular arrhythmias, ICD lead problems etc.	4 years

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Herlev and Gentofte Hospital
• Investigators: Principal Investigator: Christian Joens, MD, PhD, Dept of Cardiology, Rigshospitalet, Denmark; Study Chair: Niels Risum, MD, PhD, Dept of Cardiology, Rigshospitalet, Denmark; Study Chair: Henning Bundgaard, Prof., DMSc, Dept of Cardiology, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): February 5, 2023
• Study Completion (Anticipated): February 5, 2024

Study Registration Dates

• First Submitted: February 1, 2019
• First Submitted That Met QC Criteria: February 4, 2019
• First Posted (Actual): February 6, 2019

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Cardiac Conduction System Disease; Water-Electrolyte Imbalance; Atrial Fibrillation; Arrhythmias, Cardiac; Tachycardia; Tachycardia, Ventricular; Hyperkalemia; Hypokalemia
• Other Study ID Numbers: 3589

Drug and device information, study documents

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