October 15, 2004
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October 15, 2004
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December 1, 2014
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March 2, 2015
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March 2, 2015
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August 2006
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June 2013 (Final data collection date for primary outcome measure)
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Composite Outcome of Cardiovascular Mortality, Aborted Cardiac Arrest, or Hospitalization for the Management of Heart Failure, Whichever Occurred First [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
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Not Provided
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- Cardiovascular Mortality [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
- Aborted Cardiac Arrest [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
First incidence of aborted cardiac arrest
- Hospitalization for the Management of Heart Failure [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
First incidence of a hospitalization for the management of heart failure
- All-cause Mortality [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
- Composite Outcome of Cardiovascular Mortality or Cardiovascular-related Hospitalization (i.e., Hospitalization for Myocardial Infarction(MI), Stroke, or the Management of Heart Failure), Whichever Occurred First [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
- Cardiovascular-related Hospitalization [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Hospitalization for MI, stroke or the management of heart failure, whichever occurred first
- Total Hospitalizations (Including Repeat Hospitalizations) for the Management of Heart Failure [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
- Composite Outcome of Sudden Death or Aborted Cardiac Arrest, Whichever Occurred First [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
- New Onset Diabetes Mellitus, Among Subjects Without a History of Diabetes Mellitus at Baseline. [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
First incidence of new onset diabetes mellitus among subjects without a history of diabetes mellitus at baseline.
- Development of Atrial Fibrillation, Among Subjects Without a History of Atrial Fibrillation at Baseline. [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
First incidence of atrial fibrillation among subjects without a history of atrial fibrillation at baseline
- Myocardial Infarction [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
First incidence of myocardial infarction
- Stroke [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
First incidence of stroke
- Deterioration of Renal Function [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
First incidence of a deterioration of renal function. The TOPCAT protocol defines deterioration of renal function as occurring if a subject has a serum creatinine value which is at least double the baseline value for that subject, and is also above the upper limit of normal (assumed to be 1.0 mg/dL for females and 1.2 mg/dL for males.)
- Composite Outcome of Sudden Death, Aborted Cardiac Arrest, or Hospitalization for the Management of Ventricular Tachycardia, Whichever Occurred First [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
- Quality of Life, as Measured by the Kansas City Cardiomyopathy Questionnaire. [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline quality of life, taking into consideration baseline quality of life, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. The KCCQ was administered at the following study visits: baseline, month 4, month 12 and annually thereafter.
- Quality of Life, as Measured by the EuroQOL Visual Analog Scale. [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline quality of life, taking into consideration baseline quality of life, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
The EuroQOL visual analog scale (EQ5D) is a single-item, self-administered instrument that quantifies current health status. Scores can range from 0-100, in which higher scores reflect better health status. The EQ5D was administered at the following study visits: baseline, month 4, month 12 and annually thereafter.
- Quality of Life, as Measured by McMaster Overall Treatment Evaluation Questionnaire. [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline quality of life, taking into consideration baseline quality of life and treatment group.
The McMaster Overall Treatment Evaluation questionnaire is a self-administered 3-item instrument that measures a patient's perception of change in their health-related quality of life since the start of therapy. The questionnaire consists of a single question - "Since treatment started, has there been any change in your activity limitation, symptoms and/or feelings related to your heart condition?" Scores can range from -7 to +7, and higher scores reflect better health status. The questionnaire was administered at the following study visits: month 4 and month 12. Valid translations of this questionnaire were only available for subjects enrolled in the United States, Canada and Argentina.
- Depression Symptoms, as Measured by Patient Health Questionnaire. [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline depression, taking into consideration baseline depression, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
The Patient Health Questionnaire (PHQ) is a 10-item, self-administered instrument for screening, diagnosing, monitoring and measuring the severity of depression. Scores can range from 0-27, in which lower scores reflect better mental health status. The PH-Q was administered at the following study visits: baseline, month 12 and annually thereafter. Valid translations of this questionnaire were only available for subjects enrolled in the United States and Canada.
- Hospitalization for Any Reason [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
First incidence of a hospitalization for any reason
- Potassium [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline Potassium, taking into consideration baseline Potassium, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
- Serum Creatinine [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline serum creatinine, taking into consideration baseline serum creatinine, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
- Sodium [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline Sodium, taking into consideration baseline Sodium, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
- Chloride [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline Chloride, taking into consideration baseline Chloride, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
- Estimated Glomerular Filtration Rate (GFR) [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]
Average post-baseline GFR, taking into consideration baseline GFR, treatment group, the time between the post-baseline measures, and the correlation between repeated measures within an individual.
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Not Provided
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Not Provided
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Not Provided
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Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function
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Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)
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The purpose of this study is to evaluate the effectiveness of aldosterone antagonist therapy in reducing cardiovascular mortality, aborted cardiac arrest, and heart failure hospitalization in patients who have heart failure with preserved systolic function.
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BACKGROUND:
Heart failure (HF) is a major cause of morbidity and mortality, particularly in older people. Indeed, it is the most common discharge diagnosis in patients older than 65 years. As the United States population ages, heart failure will continue to grow as a public health concern. Therapeutic trials of heart failure have dealt almost exclusively with patients who have systolic dysfunction. However, there is now an emerging awareness that nearly half of the patients with heart failure have preserved systolic function and that the survival of these patients is adversely affected. This study is a randomized clinical trial of a novel therapeutic approach, specifically the use of spironolactone, an aldosterone antagonist, in treating these patients. While this treatment has been shown to be useful in treating heart failure with reduced systolic function, it has not been studied in patients with preserved systolic function.
Patients with heart failure and preserved systolic function have a poor prognosis. The annual mortality rate is intermediate between the prognosis for those without heart failure and for those with heart failure and reduced systolic function. For instance, Family Health Study participants with heart failure and preserved systolic function had a mortality rate of 9% compared to 3% for their age- and gender-matched controls. The mortality rate was 19% in heart failure patients with reduced systolic function heart failure compared to 4% for their matched controls.
As heart failure develops, neurohormones are released that initially improve cardiac output but ultimately contribute to progression of left ventricular dysfunction. The renin-angiotensin-aldosterone system is an important part of this compensatory response. Aldosterone levels may rise to 20 times normal levels in heart failure and aldosterone contributes to the development of myocardial fibrosis. Spironolactone is a potassium-sparing diuretic that acts on the distal tubule, inhibiting sodium and potassium ion exchange. There are several potential beneficial actions, including prevention of cardiac fibrosis. A recent trial evaluated spironolactone in patients with systolic dysfunction heart failure. Spironolactone treatment caused a 30% reduction in mortality compared to placebo (p< 0.001). The improvement resulted from a reduction in all cause mortality. More recently, the Eplerenone Post-Myocardial Infarction (MI) study showed that this aldosterone antagonist significantly reduces mortality despite background treatment with an angiotensin-converting enzyme (ACE) inhibitor and beta-blocker. Advantages of using spironolactone in this study are that it is commercially available, inexpensive, and no longer under patent (therefore this study will not be done by industry). Also, there is a clear physiologic rationale for its use, and the side effect profile is well understood. The study enrolled subjects who had preserved systolic function with heart failure and who met clearly defined eligibility criteria that were selected to make the results widely generalizable to clinical practice.
DESIGN NARRATIVE:
This is a randomized, double-blinded, placebo-controlled trial of aldosterone antagonist therapy (15 mg dose spironolactone or placebo; titrated up to 30 or 45 mg/day) in 3,445 adult patients with heart failure and preserved systolic function. Patients were recruited from August 2006 through January 2012, treated, and will be followed through June 2013. Approximately 270 clinical sites in six countries were subcontracted by the clinical trial coordinating center. Subject visits to a clinical center will occur every four or six months. Data collected include demographic and clinical data, including the results of history and physical exams, laboratory and imaging data, repository specimens for special physiology studies, and genetic studies. Additionally, data regarding quality of life and compliance with assigned treatment will also be collected and assessed.
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Treatment
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- Cardiovascular Diseases
- Heart Diseases
- Heart Failure, Congestive
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- Drug: Spironolactone
Spironolactone (an aldosterone antagonist) is supplied as 15 mg tablets. Drug is taken orally by subjects. The initial study drug dose is 15 mg/day (one tablet) and may be titrated up to 30 mg/day (two tablets) or 45 mg/day (three tablets). Subjects are on study drug for the duration of the trial.
Other Name: aldosterone antagonist
- Drug: Placebo
Placebo of spironolactone
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- Placebo Comparator: Placebo
Placebo of spironolactone
Intervention: Drug: Placebo
- Experimental: Spironolactone
Spironolactone (an aldosterone antagonist) is supplied as 15 mg tablets. Drug is taken orally by subjects. The initial study drug dose is 15 mg/day (one tablet) and may be titrated up to 30 mg/day (two tablets) or 45 mg/day (three tablets). Subjects are on study drug for the duration of the trial.
Intervention: Drug: Spironolactone
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- Lin Y, Zhong X, Liu M, Zhang S, Xiong Z, Huang Y, Fan Y, Xu X, Guo Y, Li Y, Sun X, Zhou H, Yang D, Ye X, Liao X, Zhuang X. Risk Stratification and Efficacy of Spironolactone in Patients with Heart Failure with Preserved Ejection Fraction: Secondary Analysis of the TOPCAT Randomized Clinical Trial. Cardiovasc Drugs Ther. 2022 Apr;36(2):323-331. doi: 10.1007/s10557-021-07178-y. Epub 2021 Apr 1.
- De Marco C, Claggett BL, de Denus S, Zile MR, Huynh T, Desai AS, Sirois MG, Solomon SD, Pitt B, Rouleau JL, Pfeffer MA, O'Meara E. Impact of diabetes on serum biomarkers in heart failure with preserved ejection fraction: insights from the TOPCAT trial. ESC Heart Fail. 2021 Apr;8(2):1130-1138. doi: 10.1002/ehf2.13153. Epub 2021 Jan 12.
- Shen L, Jhund PS, Anand IS, Carson PE, Desai AS, Granger CB, Køber L, Komajda M, McKelvie RS, Pfeffer MA, Solomon SD, Swedberg K, Zile MR, McMurray JJV. Developing and validating models to predict sudden death and pump failure death in patients with heart failure and preserved ejection fraction. Clin Res Cardiol. 2021 Aug;110(8):1234-1248. doi: 10.1007/s00392-020-01786-8. Epub 2020 Dec 10.
- Wu Y, Zhu W, He X, Xue R, Liang W, Wei F, Wu Z, Zhou Y, Wu D, He J, Dong Y, Liu C. Influence of polypharmacy on patients with heart failure with preserved ejection fraction: a retrospective analysis on adverse outcomes in the TOPCAT trial. Br J Gen Pract. 2020 Dec 28;71(702):e62-e70. doi: 10.3399/bjgp21X714245. Print 2021 Jan.
- Yang S, Troendle J. Event-specific win ratios and testing with terminal and non-terminal events. Clin Trials. 2021 Apr;18(2):180-187. doi: 10.1177/1740774520972408. Epub 2020 Nov 24.
- Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10:CD007004. doi: 10.1002/14651858.CD007004.pub4.
- Zhu W, Liang W, Ye Z, Wu Y, He X, Xue R, Wu Z, Zhou Y, Zhao J, Dong Y, Liu C. Association of physical activity and risk of atrial fibrillation in heart failure with preserved ejection fraction. Nutr Metab Cardiovasc Dis. 2021 Jan 4;31(1):247-253. doi: 10.1016/j.numecd.2020.08.022. Epub 2020 Aug 23.
- Chandra A, Alcala MAD, Claggett B, Desai AS, Fang JC, Heitner JF, Liu J, Pitt B, Solomon SD, Pfeffer MA, Lewis EF. Associations Between Depressive Symptoms and HFpEF-Related Outcomes. JACC Heart Fail. 2020 Dec;8(12):1009-1020. doi: 10.1016/j.jchf.2020.06.010. Epub 2020 Sep 9.
- Zhu W, Wu Y, Zhou Y, Liang W, Xue R, Wu Z, Dong Y, Liu C. CHA2DS2-VASc and ATRIA Scores and Clinical Outcomes in Patients with Heart Failure with Preserved Ejection Fraction. Cardiovasc Drugs Ther. 2020 Dec;34(6):763-772. doi: 10.1007/s10557-020-07011-y.
- Cunningham JW, Vaduganathan M, Claggett BL, John JE, Desai AS, Lewis EF, Zile MR, Carson P, Jhund PS, Kober L, Pitt B, Shah SJ, Swedberg K, Anand IS, Yusuf S, McMurray JJV, Pfeffer MA, Solomon SD. Myocardial Infarction in Heart Failure With Preserved Ejection Fraction: Pooled Analysis of 3 Clinical Trials. JACC Heart Fail. 2020 Aug;8(8):618-626. doi: 10.1016/j.jchf.2020.02.007. Epub 2020 May 6.
- Flint KM, Shah SJ, Lewis EF, Kao DP. Variation in clinical and patient-reported outcomes among complex heart failure with preserved ejection fraction phenotypes. ESC Heart Fail. 2020 Jun;7(3):811-824. doi: 10.1002/ehf2.12660. Epub 2020 Mar 11.
- Myhre PL, Vaduganathan M, O'Meara E, Claggett BL, de Denus S, Jarolim P, Anand IS, Pitt B, Rouleau JL, Solomon SD, Pfeffer MA, Desai AS. Mechanistic Effects of Spironolactone on Cardiovascular and Renal Biomarkers in Heart Failure With Preserved Ejection Fraction: A TOPCAT Biorepository Study. Circ Heart Fail. 2020 Jan;13(1):e006638. doi: 10.1161/CIRCHEARTFAILURE.119.006638. Epub 2020 Jan 20.
- Vardeny O, Claggett B, Vaduganathan M, Beldhuis I, Rouleau J, O'Meara E, Anand IS, Shah SJ, Sweitzer NK, Fang JC, Desai AS, Lewis EF, Pitt B, Pfeffer MA, Solomon SD; TOPCAT Investigators. Influence of Age on Efficacy and Safety of Spironolactone in Heart Failure. JACC Heart Fail. 2019 Dec;7(12):1022-1028. doi: 10.1016/j.jchf.2019.08.019.
- Angraal S, Mortazavi BJ, Gupta A, Khera R, Ahmad T, Desai NR, Jacoby DL, Masoudi FA, Spertus JA, Krumholz HM. Machine Learning Prediction of Mortality and Hospitalization in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2020 Jan;8(1):12-21. doi: 10.1016/j.jchf.2019.06.013. Epub 2019 Oct 9.
- Tromp J, Shen L, Jhund PS, Anand IS, Carson PE, Desai AS, Granger CB, Komajda M, McKelvie RS, Pfeffer MA, Solomon SD, Køber L, Swedberg K, Zile MR, Pitt B, Lam CSP, McMurray JJV. Age-Related Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2019 Aug 6;74(5):601-612. doi: 10.1016/j.jacc.2019.05.052.
- Beale AL, Nanayakkara S, Kaye DM. Impact of Sex on Ventricular-Vascular Stiffness and Long-Term Outcomes in Heart Failure With Preserved Ejection Fraction: TOPCAT Trial Substudy. J Am Heart Assoc. 2019 Jul 2;8(13):e012190. doi: 10.1161/JAHA.119.012190. Epub 2019 Jun 22.
- Selvaraj S, Claggett B, Shah SJ, Anand IS, Rouleau JL, Desai AS, Lewis EF, Vaduganathan M, Wang SY, Pitt B, Sweitzer NK, Pfeffer MA, Solomon SD. Utility of the Cardiovascular Physical Examination and Impact of Spironolactone in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2019 Jul;12(7):e006125. doi: 10.1161/CIRCHEARTFAILURE.119.006125. Epub 2019 Jun 21.
- Neefs J, van den Berg NWE, Krul SPJ, Boekholdt SM, de Groot JR. Effect of Spironolactone on Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: Post-Hoc Analysis of the Randomized, Placebo-Controlled TOPCAT Trial. Am J Cardiovasc Drugs. 2020 Feb;20(1):73-80. doi: 10.1007/s40256-019-00353-5.
- Kristensen SL, Mogensen UM, Jhund PS, Rørth R, Anand IS, Carson PE, Desai AS, Pitt B, Pfeffer MA, Solomon SD, Zile MR, Køber L, McMurray JJV. N-Terminal Pro-B-Type Natriuretic Peptide Levels for Risk Prediction in Patients With Heart Failure and Preserved Ejection Fraction According to Atrial Fibrillation Status. Circ Heart Fail. 2019 Mar;12(3):e005766. doi: 10.1161/CIRCHEARTFAILURE.118.005766.
- Merrill M, Sweitzer NK, Lindenfeld J, Kao DP. Sex Differences in Outcomes and Responses to Spironolactone in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of TOPCAT Trial. JACC Heart Fail. 2019 Mar;7(3):228-238. doi: 10.1016/j.jchf.2019.01.003.
- Myhre PL, O'Meara E, Claggett BL, de Denus S, Jarolim P, Anand IS, Beldhuis IE, Fleg JL, Lewis E, Pitt B, Rouleau JL, Solomon SD, Pfeffer MA, Desai AS. Cardiac Troponin I and Risk of Cardiac Events in Patients With Heart Failure and Preserved Ejection Fraction. Circ Heart Fail. 2018 Nov;11(11):e005312. doi: 10.1161/CIRCHEARTFAILURE.118.005312.
- Selvaraj S, Claggett B, Shah SJ, Anand I, Rouleau JL, O'Meara E, Desai AS, Lewis EF, Pitt B, Sweitzer NK, Fang JC, Pfeffer MA, Solomon SD. Prognostic Value of Albuminuria and Influence of Spironolactone in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2018 Nov;11(11):e005288. doi: 10.1161/CIRCHEARTFAILURE.118.005288.
- Myhre PL, Vaduganathan M, Claggett BL, Anand IS, Sweitzer NK, Fang JC, O'Meara E, Shah SJ, Desai AS, Lewis EF, Rouleau J, Pitt B, Pfeffer MA, Solomon SD. Association of Natriuretic Peptides With Cardiovascular Prognosis in Heart Failure With Preserved Ejection Fraction: Secondary Analysis of the TOPCAT Randomized Clinical Trial. JAMA Cardiol. 2018 Oct 1;3(10):1000-1005. doi: 10.1001/jamacardio.2018.2568.
- Cikes M, Claggett B, Shah AM, Desai AS, Lewis EF, Shah SJ, Anand IS, O'Meara E, Rouleau JL, Sweitzer NK, Fang JC, Saksena S, Pitt B, Pfeffer MA, Solomon SD. Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial. JACC Heart Fail. 2018 Aug;6(8):689-697. doi: 10.1016/j.jchf.2018.05.005. Epub 2018 Jul 11.
- Lewis EF, Claggett B, Shah AM, Liu J, Shah SJ, Anand I, O'Meara E, Sweitzer NK, Rouleau JL, Fang JC, Desai AS, Retta TM, Solomon SD, Heitner JF, Stamos TD, Boineau R, Pitt B, Pfeffer MA. Racial Differences in Characteristics and Outcomes of Patients With Heart Failure and Preserved Ejection Fraction in the Treatment of Preserved Cardiac Function Heart Failure Trial. Circ Heart Fail. 2018 Mar;11(3):e004457. doi: 10.1161/CIRCHEARTFAILURE.117.004457.
- Vaduganathan M, Claggett BL, Chatterjee NA, Anand IS, Sweitzer NK, Fang JC, O'Meara E, Shah SJ, Hegde SM, Desai AS, Lewis EF, Rouleau J, Pitt B, Pfeffer MA, Solomon SD. Sudden Death in Heart Failure With Preserved Ejection Fraction: A Competing Risks Analysis From the TOPCAT Trial. JACC Heart Fail. 2018 Aug;6(8):653-661. doi: 10.1016/j.jchf.2018.02.014. Epub 2018 Mar 4.
- Rossignol P, Claggett BL, Liu J, Vardeny O, Pitt B, Zannad F, Solomon S. Spironolactone and Resistant Hypertension in Heart Failure With Preserved Ejection Fraction. Am J Hypertens. 2018 Mar 10;31(4):407-414. doi: 10.1093/ajh/hpx210.
- Selvaraj S, Claggett B, Shah SJ, Anand I, Rouleau JL, Desai AS, Lewis EF, Pitt B, Sweitzer NK, Pfeffer MA, Solomon SD. Systolic blood pressure and cardiovascular outcomes in heart failure with preserved ejection fraction: an analysis of the TOPCAT trial. Eur J Heart Fail. 2018 Mar;20(3):483-490. doi: 10.1002/ejhf.1060. Epub 2017 Nov 16.
- Pokharel Y, Khariton Y, Tang Y, Nassif ME, Chan PS, Arnold SV, Jones PG, Spertus JA. Association of Serial Kansas City Cardiomyopathy Questionnaire Assessments With Death and Hospitalization in Patients With Heart Failure With Preserved and Reduced Ejection Fraction: A Secondary Analysis of 2 Randomized Clinical Trials. JAMA Cardiol. 2017 Dec 1;2(12):1315-1321. doi: 10.1001/jamacardio.2017.3983. Erratum in: JAMA Cardiol. 2018 Feb 1;3(2):181.
- Hegde SM, Claggett B, Shah AM, Lewis EF, Anand I, Shah SJ, Sweitzer NK, Fang JC, Pitt B, Pfeffer MA, Solomon SD. Physical Activity and Prognosis in the TOPCAT Trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). Circulation. 2017 Sep 12;136(11):982-992. doi: 10.1161/CIRCULATIONAHA.117.028002. Epub 2017 Jun 21.
- Anand IS, Claggett B, Liu J, Shah AM, Rector TS, Shah SJ, Desai AS, O'Meara E, Fleg JL, Pfeffer MA, Pitt B, Solomon SD. Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial. JACC Heart Fail. 2017 Apr;5(4):241-252. doi: 10.1016/j.jchf.2016.11.015.
- Biering-Sørensen T, Shah SJ, Anand I, Sweitzer N, Claggett B, Liu L, Pitt B, Pfeffer MA, Solomon SD, Shah AM. Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction. Eur J Heart Fail. 2017 Aug;19(8):1043-1052. doi: 10.1002/ejhf.789. Epub 2017 Mar 21.
- Santos AB, Roca GQ, Claggett B, Sweitzer NK, Shah SJ, Anand IS, Fang JC, Zile MR, Pitt B, Solomon SD, Shah AM. Prognostic Relevance of Left Atrial Dysfunction in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2016 Apr;9(4):e002763. doi: 10.1161/CIRCHEARTFAILURE.115.002763.
- Joseph J, Claggett BC, Anand IS, Fleg JL, Huynh T, Desai AS, Solomon SD, O'Meara E, Mckinlay S, Pitt B, Pfeffer MA, Lewis EF. QRS Duration Is a Predictor of Adverse Outcomes in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2016 Jun;4(6):477-86. doi: 10.1016/j.jchf.2016.02.013. Epub 2016 Mar 30.
- Lewis EF, Kim HY, Claggett B, Spertus J, Heitner JF, Assmann SF, Kenwood CT, Solomon SD, Desai AS, Fang JC, McKinlay SA, Pitt BA, Pfeffer MA; TOPCAT Investigators. Impact of Spironolactone on Longitudinal Changes in Health-Related Quality of Life in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial. Circ Heart Fail. 2016 Mar;9(3):e001937. doi: 10.1161/CIRCHEARTFAILURE.114.001937.
- Shah AM, Claggett B, Sweitzer NK, Shah SJ, Deswal A, Anand IS, Fleg JL, Pitt B, Pfeffer MA, Solomon SD. Prognostic Importance of Changes in Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone. Circ Heart Fail. 2015 Nov;8(6):1052-8. doi: 10.1161/CIRCHEARTFAILURE.115.002249. Epub 2015 Oct 16.
- Solomon SD, Claggett B, Lewis EF, Desai A, Anand I, Sweitzer NK, O'Meara E, Shah SJ, McKinlay S, Fleg JL, Sopko G, Pitt B, Pfeffer MA; TOPCAT Investigators. Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction. Eur Heart J. 2016 Feb 1;37(5):455-62. doi: 10.1093/eurheartj/ehv464. Epub 2015 Sep 15.
- Shah AM, Claggett B, Sweitzer NK, Shah SJ, Anand IS, Liu L, Pitt B, Pfeffer MA, Solomon SD. Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone. Circulation. 2015 Aug 4;132(5):402-14. doi: 10.1161/CIRCULATIONAHA.115.015884. Epub 2015 Jun 30.
- Borlaug BA, Lewis GD, McNulty SE, Semigran MJ, LeWinter M, Chen H, Lin G, Deswal A, Margulies KB, Redfield MM. Effects of sildenafil on ventricular and vascular function in heart failure with preserved ejection fraction. Circ Heart Fail. 2015 May;8(3):533-41. doi: 10.1161/CIRCHEARTFAILURE.114.001915. Epub 2015 Mar 17.
- Hamo CE, Heitner JF, Pfeffer MA, Kim HY, Kenwood CT, Assmann SF, Solomon SD, Boineau R, Fleg JL, Spertus JA, Lewis EF. Baseline distribution of participants with depression and impaired quality of life in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial. Circ Heart Fail. 2015 Mar;8(2):268-77. doi: 10.1161/CIRCHEARTFAILURE.114.001838. Epub 2015 Feb 3.
- Mak GJ, Ledwidge MT, Watson CJ, Phelan DM, Dawkins IR, Murphy NF, Patle AK, Baugh JA, McDonald KM. Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone. J Am Coll Cardiol. 2009 Oct 27;54(18):1674-82. doi: 10.1016/j.jacc.2009.08.021.
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Completed
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3445
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Not Provided
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June 2013
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June 2013 (Final data collection date for primary outcome measure)
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INCLUSION CRITERIA:
- Heart failure as defined by at least one of symptom (paroxysmal nocturnal dyspnea; orthopnea; or dyspnea on mild or moderate exertion) at the time of screening and at least one sign (any rales post cough; jugular venous pressure(JVP) greater than or equal to 10cm of water(H2O); lower extremity edema; or chest x-ray demonstrating pleural effusion, pulmonary congestion, or cardiomegaly) within 12 months prior to study entry:
- left ventricular ejection fraction greater than or equal to 45% (per local reading); the ejection fraction must have been obtained within 6 months prior to randomization and after any MI or other event that would affect ejection fraction
- Controlled systolic blood pressure(BP), defined as a target systolic BP less than 140 mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment if they are on three or more medications to control BP
- Serum potassium less than 5.0 mmol/L prior to randomization
- At least one hospital admission for which heart failure was a major component of the hospitalization some time within the 12 months prior to study entry OR brain natriuretic peptide (BNP) greater than or equal to 100pg/ml or N-terminal pro-BNP greater than or equal to 360pg/ml within the 60 days prior to study entry
- Women of child-bearing potential must have a negative serum/urine pregnancy test within 72 hours prior to randomization, must not be lactating, and must agree to use an effective method of contraception during the entire course of study participation
- Willing to comply with scheduled visits
- Informed consent form signed by the subject prior to participation in the trial
EXCLUSION CRITERIA:
- Severe systemic illness with an expected life expectancy of less than 3 years
- Chronic pulmonary disease requiring home O2, oral steroid therapy, or hospitalization for exacerbation within 12 months of study entry, or significant chronic pulmonary disease in the opinion of the investigator
- Known infiltrative or hypertrophic obstructive cardiomyopathy or known pericardial constriction
- Primary hemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant, or any valvular disease expected to lead to surgery during the trial
- Atrial fibrillation with a resting heart rate greater than 90 bpm
- MI in the past 90 days
- Coronary artery bypass graft surgery in the past 90 days
- Percutaneous coronary intervention in the past 30 days
- Heart transplant recipient
- Currently implanted left ventricular assist device
- Stroke in past 90 days
- Systolic BP (SBP) greater than 160 mm Hg
- Known orthostatic hypotension
- Gastrointestinal disorder that could interfere with study drug absorption
- Use of any aldosterone antagonist or potassium sparing medication in the last 14 days or any known condition that would require the use of an aldosterone antagonist during study participation;
- Known intolerance to aldosterone antagonists
- Current lithium use
- Current participation (including prior 30 days) in any other therapeutic trial
- Any condition that, in the opinion of the investigator, may prevent the participant from adhering to the trial protocol
- History of hyperkalemia (serum potassium greater than or equal to 5.5mmol/L) in the past 6 months or serum potassium greater than or equal to 5.0mmol/L within the past 2 weeks
- Severe renal dysfunction, defined as an estimated glomerular filtration rate(GFR) less than 30ml/min. Participants with serum creatinine greater than or equal to 2.5mg/dl are also excluded even if their GFR is greater than or equal to 30ml/min
- Known chronic hepatic disease, defined as aspartate aminotransferase(AST) and alanine aminotransferase(ALT) levels greater than 3.0 times the upper limit of normal as read at the local lab.
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Sexes Eligible for Study: |
All |
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50 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Argentina, Brazil, Canada, Georgia, Russian Federation, United States
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NCT00094302
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160 HHSN268200425207C ( Other Grant/Funding Number: NIH contract )
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Yes
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Not Provided
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Not Provided
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HealthCore-NERI
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Not Provided
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HealthCore-NERI
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National Heart, Lung, and Blood Institute (NHLBI)
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National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: |
Sonja M. McKinlay, PhD |
New England Research Institutes, Inc. |
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HealthCore-NERI
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January 2014
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