Antiarrhythmic Effects of Spironolactone in Patients With ICDs (SPIRIT)

October 7, 2020 updated by: VA Office of Research and Development
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • VA Portland Health Care System, Portland, OR

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Spironolactone
Patients randomized to active therapy with spironolactone
Drug: spironolactone
aldosterone blocker
Other Names:
  • Aldactone
Placebo Comparator: placebo
patients randomized to placebo
Drug: placebo
identical in appearance to spironolactone study drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to First Appropriate Implantable Cardioverter Defibrillator (ICD) Therapy
Time Frame: through study completion, an average of 35 months
Time to first documented ICD therapy for ventricular tachycardia or ventricular fibrillation after randomization
through study completion, an average of 35 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All Cause Hospitalization
Time Frame: through study completion, an average of 35 months
Number of patients hospitalized for any reason during study follow-up.
through study completion, an average of 35 months
Ventricular Refractoriness
Time Frame: measured 3 months after randomization
The right ventricular effective refractory period (ERP) will be measured at 3 month in patients enrolled at the Portland VA Medical Center by single extra stimuli via their implanted defibrillator. The ERP is defined as the shortest paced beat coupling interval that fails to produce ventricular capture after a baseline stable pacing train.
measured 3 months after randomization
Short Form Health Survey Adapted for Veterans (SF36V)
Time Frame: 12 months after enrollment
Short Form Health Survey adapted for veterans (SF36V) is a 36 item questionnaire that measures general physical and mental health [17]. The SF36V is a reliable and valid questionnaire, containing eight constructs of health status: physical functioning (PF), role limitations due to physical problems (RP), bodily pain (BP), general health perceptions (GH), energy/vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). These eight dimensions can be summarized numerically into two scores, the physical component summary (PCS) and the mental component summary (MCS). Range 0-100 higher score is better Health Related Quality of Life (HRQOL). We are reporting the Mental Component Summary score at 12 months here.
12 months after enrollment
Patient Concerns Assessment (PCA)
Time Frame: 12 months
Patient Concerns Assessment (PCA) is a symptom checklist that measures physical symptoms and fears that are common after ICD implantation. The PCA is a disease-specific instrument for ICD QOL, symptoms, and distress, with a reliability of ( = 0.88). Range 0-44, a higher score reflects more concerns and fears.
12 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame: through study completion, an average of 35 months
Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item reliable and valid questionnaire, which evaluates HRQOL in heart failure. It quantifies, in a disease-specific fashion, physical limitations, symptoms, quality of life, social interference and self-efficacy. KCCQ provides the calculation of 2 main scores, the overall score and the clinical summary score, which includes functional status, social limitation and quality of life domains scores. Range 0-100, higher scores represent higher HRQOL.
through study completion, an average of 35 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Merritt Raitt, MD, VA Portland Health Care System, Portland, OR

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 28, 2004

Primary Completion (Actual)

May 28, 2008

Study Completion (Actual)

May 28, 2008

Study Registration Dates

First Submitted

July 28, 2020

First Submitted That Met QC Criteria

July 28, 2020

First Posted (Actual)

August 3, 2020

Study Record Updates

Last Update Posted (Actual)

October 9, 2020

Last Update Submitted That Met QC Criteria

October 7, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICDAD-1
  • VA 02-2704 (Other Grant/Funding Number: Department of Defene and VA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Patients did not give permission for data sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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