Antiarrhythmic Effects of Spironolactone in Patients With ICDs

NCT04495712 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: ICDAD-1VA 02-2704
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Ventricular Arrhythmias

Keywords

Anti-Arrhythmia Agents; Ventricular Fibrillation; Ventricular Tachycardia; Defibrillators, Implantable

Outcome Measures

Primary Outcomes (1)

• Time to First Appropriate Implantable Cardioverter Defibrillator (ICD) Therapy

  Time to first documented ICD therapy for ventricular tachycardia or ventricular fibrillation after randomization

  through study completion, an average of 35 months

Secondary Outcomes (5)

• All Cause Hospitalization

  through study completion, an average of 35 months

• Ventricular Refractoriness

  measured 3 months after randomization

• Short Form Health Survey Adapted for Veterans (SF36V)

  12 months after enrollment

• Patient Concerns Assessment (PCA)

  12 months

• Kansas City Cardiomyopathy Questionnaire (KCCQ)

  through study completion, an average of 35 months

Study Arms (2)

Spironolactone

ACTIVE COMPARATOR

Patients randomized to active therapy with spironolactone

Drug: spironolactone

placebo

PLACEBO COMPARATOR

patients randomized to placebo

Drug: placebo

Interventions

spironolactone DRUG

aldosterone blocker

Also known as: Aldactone

Spironolactone

placebo DRUG

identical in appearance to spironolactone study drug

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97239, United States

Location

Related Publications (2)

• 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.

  PMID: 22773022 RESULT

• 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.

  PMID: 34362264 DERIVED

MeSH Terms

Conditions

Ventricular Fibrillation; Tachycardia, Ventricular

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Tachycardia; Cardiac Conduction System Disease

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

A limitation of this study was its small sample size. If a 35% relative risk reduction in the primary end point were assumed, the sample size of this trial would have given it 76% power with a type I error rate of 0.05.

Results Point of Contact

• Title: Merritt Raitt MD
• Organization: VA Portland Health Care System

merritt.raitt@va.gov

503-220-8262

Study Officials

• Merritt Raitt, MD

  VA Portland Health Care System, Portland, OR

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All participants, providers, investigators, and outcome assessors were blinded to treatment assignment. The pharmacy maintained a key to randomization that was not broken until the study was completed and all outcomes had been assessed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This was a prospective, double-blind, randomized trial that assigned patients to receive either spironolactone 25 mg/day or a placebo.

Study Record Dates

• First Submitted: July 28, 2020
• First Posted: August 3, 2020
• Study Start: July 28, 2004
• Primary Completion: May 28, 2008
• Study Completion: May 28, 2008
• Last Updated: October 9, 2020
• Results First Posted: September 4, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)