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This is a prospective, single-center, double-blind and randomized placebo controlled trial for evaluation of a 7-day 100mg daily dose of spironolactone on weight loss and resolution of signs and symptoms of congestion in outpatients with acute decompensated heart failure (ADHF). Patients who are not responding to their current loop diuretics will be considered for this study. Mineralocorticoid receptor antagonists (MRAs) are recommended as standard of care in management of heart failure (HF) patients. However, recommended doses of MRAs (spironolactone 25mg/daily or eplerenone 50mg/daily) will not have any impact on signs and symptoms of volume overload. Therefore, the proposed study will aim to show the impact of this outpatient regimen to improve diuresis and possible reduction in hospitalization for further diuretic management in HF patients with signs and symptoms of congestion.
The incidence and prevalence of heart failure (HF) is rising with more than 5 million Americans suffering from this syndrome. Hospitalization rates for acute decompensated heart failure (ADHF) are also remarkably high, exceeding more than 1 million admissions per year. Congestion is the main cause of hospitalization for ADHF. Loop diuretics as the main therapy for decongestion, often are not adequate since many patients with ADHF develop "loop diuretic resistance". These patients will require hospitalization for intravenous diuretic or other advanced decongestion therapies. Thus, novel decongestion therapies are needed to decrease hospital admission rates and subsequent complications of multiple hospitalizations. Hyperaldosteronism, not only is a pivotal pathogenic factor in HF, but also contributes to loop diuretic resistance. Attempts for normalization of circulatory aldosterone with mineralocorticoid receptor antagonists (MRAs), mainly spironolactone, have shown to decrease mortality in HF patients with reduced left ventricular ejection fraction (LVEF). Moreover, MRAs significantly decrease the rate of rehospitalization in both HF with preserved and reduced LVEF. The dose of spironolactone in these trials is 25mg daily. However, this dose does not increase natriuresis (urinary sodium excretion). Natriuresis is achieved with higher doses of MRAs. Therefore, the primary aim of this study is to examine the efficacy of 7-day 100mg daily of spironolactone on weight loss and resolution of signs and symptoms of congestion in patients aged 60 years with ADHF and loop diuretic resistance.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-dose | Experimental | Spironolactone 100mg: 100mg/day of spironolactone (2 capsules), PO (oral) for 7 days |
|
| Standard of Care | Active Comparator | Spironolactone 25mg: 25mg/day of spironolactone, PO (oral) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Spironolactone 100mg | Drug | 2 capsules of study medication consist of 100mg, PO (oral) for 7 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Body Weight | change in body weight measured in kilograms between weight at baseline and weight at 7 days | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Estimated Jugular Venous Pressure (cmH2O) | Change in estimated jugular venous pressure by physical exam in cmH2O between baseline and 7 days | 7 days |
| Change in 6-minute Walk Test Distance (6MWT) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Arthur R Garan, MD | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Medical Center | New York | New York | 10032 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | High-dose | Spironolactone 100mg: 100mg/day of spironolactone (2 capsules), PO (oral) for 7 days Spironolactone 100mg: 2 capsules of study medication consist of 100mg, PO (oral) for 7 days |
| FG001 | Standard of Care | Spironolactone 25mg: 25mg/day of spironolactone, PO (oral) Spironolactone 25mg: 25mg/day of spironolactone |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | High-dose | Spironolactone 100mg: 100mg/day of spironolactone (2 capsules), PO (oral) for 7 days Spironolactone 100mg: 2 capsules of study medication consist of 100mg, PO (oral) for 7 days |
| BG001 | Standard of Care |
| 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 | Change in Body Weight | change in body weight measured in kilograms between weight at baseline and weight at 7 days | Posted | Mean | Standard Deviation | kilogram | 7 days |
|
12 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 | High-dose | Spironolactone 100mg: 100mg/day of spironolactone (2 capsules), PO (oral) for 7 days Spironolactone 100mg: 2 capsules of study medication consist of 100mg, PO (oral) for 7 days |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperkalemia | Renal and urinary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| A. Reshad Garan | Columbia University | (917) 374-3346 | arg2024@cumc.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 30, 2015 | Jun 28, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 30, 2015 | Jun 28, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D002191 | Canrenoic Acid |
| D013148 | Spironolactone |
| ID | Term |
|---|---|
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| Spironolactone 25mg | Drug | 25mg/day of spironolactone |
|
|
At baseline and final visit. The 6MWT will be conducted per American Thoracic Society guidelines.
| 7 days |
| Change in Score on the Visual Analogue Scale (VAS) | Dyspnea will be assessed at baseline and at 7 days with the score on the visual analogue scale (VAS). The scores range from 0 (minimum) to 100 (maximum) with higher numbers representing improvements in dyspnea (i.e. better) and lower numbers representing worsening of dyspnea (i.e. worse). | 7 days |
| Change From Baseline to Day 7 on the Seven-Level Likert Scale | Dyspnea will be assessed using a Seven-Level Likert Scale at baseline and the day 7 visit. The outcome measure will be reported as a difference between these two assessments (value at 7 days minus the value at baseline). The values on this scale range from 1 to 7 with higher numbers indicating overall better subjective assessment related to the symptom of dyspnea. Therefore, positive numbers represent an overall improvement in dyspnea during the study intervention and the higher (more positive) this difference is, the better the subject's relief of dyspnea at the conclusion of the study intervention. | 7 days |
Spironolactone 25mg: 25mg/day of spironolactone, PO (oral)
Spironolactone 25mg: 25mg/day of spironolactone
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Baseline 6 minute walk test | Mean | Standard Deviation | meters |
|
| Units | Counts |
|---|
| Participants |
|
|
| Secondary | Change in Estimated Jugular Venous Pressure (cmH2O) | Change in estimated jugular venous pressure by physical exam in cmH2O between baseline and 7 days | Posted | Mean | Standard Deviation | cmH2O | 7 days |
|
|
|
| Secondary | Change in 6-minute Walk Test Distance (6MWT) | At baseline and final visit. The 6MWT will be conducted per American Thoracic Society guidelines. | Posted | Mean | Standard Deviation | meters | 7 days |
|
|
|
| Secondary | Change in Score on the Visual Analogue Scale (VAS) | Dyspnea will be assessed at baseline and at 7 days with the score on the visual analogue scale (VAS). The scores range from 0 (minimum) to 100 (maximum) with higher numbers representing improvements in dyspnea (i.e. better) and lower numbers representing worsening of dyspnea (i.e. worse). | Posted | Mean | Standard Deviation | units on a scale | 7 days |
|
|
|
| Secondary | Change From Baseline to Day 7 on the Seven-Level Likert Scale | Dyspnea will be assessed using a Seven-Level Likert Scale at baseline and the day 7 visit. The outcome measure will be reported as a difference between these two assessments (value at 7 days minus the value at baseline). The values on this scale range from 1 to 7 with higher numbers indicating overall better subjective assessment related to the symptom of dyspnea. Therefore, positive numbers represent an overall improvement in dyspnea during the study intervention and the higher (more positive) this difference is, the better the subject's relief of dyspnea at the conclusion of the study intervention. | Posted | Mean | Standard Deviation | units on a scale | 7 days |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 1 |
| 10 |
| EG001 | Standard of Care | Spironolactone 25mg: 25mg/day of spironolactone, PO (oral) Spironolactone 25mg: 25mg/day of spironolactone | 0 | 10 | 0 | 10 | 0 | 10 |
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| D011083 |
| Polycyclic Compounds |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |