Clinical trial NCT04495712: Antiarrhythmic Effects of Spironolactone in Patients With ICDs
Official title: Antiarrhythmic Effects of Spironolactone in Patients With ICDs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ventricular Arrhythmias
Keywords: Anti-Arrhythmia Agents
Ventricular Fibrillation
Ventricular Tachycardia
Defibrillators, Implantable
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2020-08-03
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a prospective, double-blind, randomized trial that assigned patients to receive either spironolactone 25 mg/day or a placebo.
Primary purpose: TREATMENT

Brief summary: This study will test whether spironolactone, an approved drug for among other things hypertension, will reduce the risk of severe arrhythmias in patients with implanted defibrillators. Half the patients in the study will get spironolactone and half will get a placebo. Neither the patients or their providers will know if they are getting spironolactone or placebo.

Detailed description: Objectives: This study is designed to determine whether spironolactone at a dose of 25 mg per day in patients with implanted cardioverter defibrillators (ICD) will 1) Reduce the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF), 2) Improve health related quality of life, 3) Reduce the need for hospitalization, and 4) Change ventricular refractoriness.

Plan: The study was a randomized double blind placebo controlled multi-center trial. Patients were randomized to either 25 mg per day of spironolactone or placebo and followed for 2 years each. The primary endpoint is time to the first episode of VT/VF. Secondary endpoints will include changes in health related quality of life, frequency of hospitalization, and in a subset of patients the effect of spironolactone on the ventricular effective refractory period measured through the ICD 3 months after starting the study medication. All data analyses will be conducted on intent to treat basis.

Methods: Patients were recruited at the Portland VA ICD clinics, the Seattle VA ICD clinics, Oregon Health and Sciences University ICD clinics and the Little Rock, Arkansas VA ICD clinics. Randomization and drug preparation were done by the Portland VA Medical Center research pharmacy. For safety purposes serum potassium will be measured at 1, 2, 3, 6, 12, 18, and 24 months. Patients will undergo ICD interrogation to document the occurrence of ICD therapy for VT or VF and will be screened for potential drug side effects every 3 months during the study. Health related quality of life will be measured at baseline, 3, 6, 12, 18, and 24 months using Short Form Health Survey adapted for veterans (SF36V) Veterans Health Study Version, the Patients Concerns Assessment, and the Kansas City Cardiomyopathy Questionnaire. Hospitalizations will be tracked throughout the study. In the subset of patient enrolled at the Portland VA the ventricular effective refractory period will be measured via single extra stimuli pacing through the ICD at 3 months after randomization.

Eligibility criteria: Inclusion Criteria:

-Patients were considered eligible for enrollment only if they had received

* an ICD therapy, either a shock or antitachycardia pacing (ATP),
* VT/VF in the previous 2 years or
* received an ICD for secondary prevention of sustained VT/VF in the previous 6 months.

Exclusion Criteria:

-Important exclusion criteria were

* an indication for spironolactone based on the RALES trial (EF of \<35% and -New York Heart Association (NYHA) class III or IV),
* unstable angina,
* primary hepatic failure,
* known intolerance to spironolactone,
* a serum creatinine concentration of \>2.5 mg/dL,
* a serum potassium concentration of \>5.0 mmol/L, and
* a life expectancy of \<2 years.

Primary outcomes:
measure: Time to First Appropriate Implantable Cardioverter Defibrillator (ICD) Therapy
timeFrame: through study completion, an average of 35 months
Secondary outcomes:
measure: All Cause Hospitalization
timeFrame: through study completion, an average of 35 months
measure: Ventricular Refractoriness
timeFrame: measured 3 months after randomization
measure: Short Form Health Survey Adapted for Veterans (SF36V)
timeFrame: 12 months after enrollment
measure: Patient Concerns Assessment (PCA)
timeFrame: 12 months
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: through study completion, an average of 35 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: VA Portland Health Care System, Portland, OR
state: Oregon
Study officials:
affiliation: VA Portland Health Care System, Portland, OR
name: Merritt Raitt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zarraga IG, Dougherty CM, MacMurdy KS, Raitt MH. The effect of spironolactone on ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators. Circ Arrhythm Electrophysiol. 2012 Aug 1;5(4):739-47. doi: 10.1161/CIRCEP.112.970566. Epub 2012 Jul 7.
citation: Liberato ACS, Raitt MH, Zarraga IGE, MacMurdy KS, Dougherty CM. Health-Related Quality of Life in the Spironolactone to Reduce ICD Therapy (SPIRIT) Trial. Clin Nurs Res. 2022 May;31(4):588-597. doi: 10.1177/10547738211036817. Epub 2021 Aug 6.