Targeted Potassium Levels for Prevention of ICD Therapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Arrhythmia Prevention in High Risk Cardiovascular Patients Using Targeted Potassium Levels

Conditions
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Ventricular Arrhythmias and Cardiac Arrest, Implantable Defibrillator User, Hypokalemia, Hyperkalemia, Ventricular Tachycardia, Atrial Fibrillation

Intervention / Treatment
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* Combination Product: Targeted serum potassium level


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>ICD recipients in optimal Medical treatment as per guidelines according to their comorbidity | |
| Experimental: Targeted serum potassium levels<br>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<br>* In the following order, following advices end prescriptions will be provided: 1) Potassium rich dietary advice, 2) Potassium supplementation, 3) mineralocorticoid receptor antagonists,<br>|

What is the study measuring?
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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 |