A Phase 4 interventional study of spironolactone and placebo in Ventricular Arrhythmias, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-10-09.
Sponsored by VA Office of Research and Development · Phase 4, Interventional, and Treatment
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.
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.
885 studies on the registry are indexed under Arrhythmias, Cardiac; 235 are open to participants now.
This study's enrollment of 90 is close to the median of 99 across 429 interventional studies indexed under Arrhythmias, Cardiac.
Browse Arrhythmias, Cardiac studies →VA Office of Research and Development is the lead sponsor of 1,733 studies on the registry; 396 are open to participants now.
Of its 206 completed or terminated interventional studies of FDA-regulated products, 180 (87%) have results posted.
Counted across the registry records on this site, refreshed daily.
-Patients were considered eligible for enrollment only if they had received
Exclusion Criteria:
-Important exclusion criteria were
Patients randomized to active therapy with spironolactone
Drug: spironolactone
patients randomized to placebo
Drug: placebo
aldosterone blocker
Also known as: Aldactone
identical in appearance to spironolactone study drug
Time to First Appropriate Implantable Cardioverter Defibrillator (ICD) Therapy
Time to first documented ICD therapy for ventricular tachycardia or ventricular fibrillation after randomization
Time frame: through study completion, an average of 35 months
All Cause Hospitalization
Number of patients hospitalized for any reason during study follow-up.
Time frame: through study completion, an average of 35 months
Ventricular Refractoriness
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.
Time frame: measured 3 months after randomization
Short Form Health Survey Adapted for Veterans (SF36V)
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.
Time frame: 12 months after enrollment
Patient Concerns Assessment (PCA)
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.
Time frame: 12 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)
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.
Time frame: through study completion, an average of 35 months
| Milestone | Spironolactone | Placebo |
|---|---|---|
| Started | 44 | 46 |
| Completed | 44 | 46 |
| Not completed | 0 | 0 |
Time to first documented ICD therapy for ventricular tachycardia or ventricular fibrillation after randomization
| months | Spironolactone | Placebo |
|---|---|---|
| Time to First Appropriate Implantable Cardioverter Defibrillator (ICD) Therapy | 8.8 (0 to 37.2) | 12.3 (0.3 to 38.5) |
Number of patients hospitalized for any reason during study follow-up.
| Participants | Spironolactone | Placebo |
|---|---|---|
| All Cause Hospitalization | 28 | 24 |
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.
| milliseconds | Spironolactone | Placebo |
|---|---|---|
| Ventricular Refractoriness | 294.2 ± 40.8 | 278.3 ± 24.1 |
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.
| score on a scale | Spironolactone | Placebo |
|---|---|---|
| Short Form Health Survey Adapted for Veterans (SF36V) | 54.87 ± 22.50 | 63.31 ± 20.35 |
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.
| score on a scale | Spironolactone | Placebo |
|---|---|---|
| Patient Concerns Assessment (PCA) | 22.15 ± 12.28 | 18.42 ± 10.06 |
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.
| score on a scale | Spironolactone | Placebo |
|---|---|---|
| Kansas City Cardiomyopathy Questionnaire (KCCQ) | 57.35 ± 28.59 | 68.67 ± 22.55 |
Collected over life of the study mean 35 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Spironolactone | 13/44 (29.5%) | 39/44 (88.6%) | 44/44 (100%) |
| Placebo | 12/46 (26.1%) | 37/46 (80.4%) | 46/46 (100%) |
| Event | Spironolactone | Placebo |
|---|---|---|
| hospitalizationGeneral disorders | 38/44 | 35/46 |
| deathGeneral disorders | 13/44 | 12/46 |
| Event | Spironolactone | Placebo |
|---|---|---|
| congestive heart failureCardiac disorders | 34/44 | 33/46 |
| Any gastrointestinal issueGastrointestinal disorders | 25/44 | 22/46 |
| Prerenal azotemiaRenal and urinary disorders | 16/44 | 11/46 |
| GynecomastiaEndocrine disorders | 4/44 | 0/46 |
| Age, Continuous(years) | Spironolactone | Placebo | Total |
|---|---|---|---|
| Mean | 66.6 ± 10.9 | 66.5 ± 9.3 | 66.5 ± 10.0 |
| Sex: Female, Male(Participants) | Spironolactone | Placebo | Total |
|---|---|---|---|
| Female | 44 | 42 | 86 |
| Male | 0 | 4 | 4 |
| Race and Ethnicity Not Collected(Participants) | Spironolactone | Placebo | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(Participants) | Spironolactone | Placebo | Total |
|---|---|---|---|
| United States | 44 | 46 | 90 |
Plan to share: No — Patients did not give permission for data sharing
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