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| ID | Type | Description | Link |
|---|---|---|---|
| VA 02-2704 | Other Grant/Funding Number | Department of Defene and VA |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Spironolactone | Active Comparator | Patients randomized to active therapy with spironolactone |
|
| placebo | Placebo Comparator | patients randomized to placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| spironolactone | Drug | aldosterone blocker |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| All Cause Hospitalization | Number of patients hospitalized for any reason during study follow-up. | 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. |
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Inclusion Criteria:
-Patients were considered eligible for enrollment only if they had received
Exclusion Criteria:
-Important exclusion criteria were
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| Name | Affiliation | Role |
|---|---|---|
| Merritt Raitt, MD | VA Portland Health Care System, Portland, OR | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Portland Health Care System, Portland, OR | Portland | Oregon | 97239 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22773022 | Result | 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. | |
| 34362264 | Derived | 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. |
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Patients did not give permission for data sharing
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| ID | Title | Description |
|---|---|---|
| FG000 | Spironolactone | Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker |
| FG001 | Placebo | patients randomized to placebo placebo: identical in appearance to spironolactone study drug |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Spironolactone | Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker |
| BG001 | Placebo | patients randomized to placebo placebo: identical in appearance to spironolactone study drug |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to First Appropriate Implantable Cardioverter Defibrillator (ICD) Therapy | Time to first documented ICD therapy for ventricular tachycardia or ventricular fibrillation after randomization | all enrolled patients | Posted | Median | Full Range | months | through study completion, an average of 35 months |
|
life of the study mean 35 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Spironolactone | Patients randomized to active therapy with spironolactone spironolactone: aldosterone blocker |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hospitalization | General disorders | Systematic Assessment | hospitalization for any cause |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gynecomastia | Endocrine disorders | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merritt Raitt MD | VA Portland Health Care System | 503-220-8262 | 57571 | merritt.raitt@va.gov |
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| ID | Term |
|---|---|
| D014693 | Ventricular Fibrillation |
| D017180 | Tachycardia, Ventricular |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D013148 | Spironolactone |
| ID | Term |
|---|---|
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 |
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This was a prospective, double-blind, randomized trial that assigned patients to receive either spironolactone 25 mg/day or a placebo.
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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.
| placebo | Drug | identical in appearance to spironolactone study drug |
|
| 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. | 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. | 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. | through study completion, an average of 35 months |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Secondary | All Cause Hospitalization | Number of patients hospitalized for any reason during study follow-up. | all randomized patients | Posted | Count of Participants | Participants | through study completion, an average of 35 months |
|
|
|
|
| Secondary | 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. | Patients randomized at the Portland VA Hospital that consented to testing | Posted | Mean | Standard Deviation | milliseconds | measured 3 months after randomization |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 12 months after enrollment |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 12 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | through study completion, an average of 35 months |
|
|
|
| 13 |
| 44 |
| 39 |
| 44 |
| 44 |
| 44 |
| EG001 | Placebo | patients randomized to placebo placebo: identical in appearance to spironolactone study drug | 12 | 46 | 37 | 46 | 46 | 46 |
|
| death | General disorders | Systematic Assessment |
|
| congestive heart failure | Cardiac disorders | Systematic Assessment |
|
| Prerenal azotemia | Renal and urinary disorders | Systematic Assessment |
|
| Any gastrointestinal issue | Gastrointestinal disorders | Systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D013610 | Tachycardia |
| D000075224 | Cardiac Conduction System Disease |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |