Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) - Catalog
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Name
Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)
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Accession Number
HLB01341624a
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Acronym
TOPCAT
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Related studies
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BSI Study IDs
TCT
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Is public use dataset
False
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Keywords
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Ingestion StatusReleased
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Has Study Datasets
True
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Has Specimens
True
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Specimen ID TypeCoded
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Study Website
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The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.
False
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Clinical Trial URLs
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Study typeClinical Trial
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Collection TypeOpen BioLINCC Study
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Cohort typeAdult
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Interventions
Drug: SpironolactoneDrug: Placebo
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Study Open Date (Data)
2016-04-13
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Study Open Date (Specimens)
2016-04-13
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Date materials available
2011-08-04
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Last updated
2016-04-12
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Study period
August 2006 – June 2013
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Study Contacts
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NHLBI Division
DCVS
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ClassificationHeart
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HIV study classificationnon-HIV
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COVID study classificationnon-COVID
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Pre-Website # of Specimens Shipped
0
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# of Returned Specimens
0
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Primary Publication URLs
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Commercial use data restrictionsNo
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Data restrictions based on area of researchNo
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Commercial use specimen restrictionsNo
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Non-genetic use specimen restrictions based on area of useNo
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Genetic use of specimens allowed?Yes, For Some Specimens
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Genetic use area of research restrictionsYes
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Specific Consent Restrictions
Consent for the use of biospecimens in genetic research is tiered to (1) research related to heart disease, stroke, kidney diseases, other cardiovascular diseases, or risk factors associated with these diseases and (2) research related to any disease, health condition or risk factors. Use of biospecimens in non-genetic research is unrestricted.
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ConditionsCardiovascular Diseases
Heart Diseases
Heart Failure, Congestive
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Objectives
The TOPCAT trial evaluated 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
Many patients with heart failure have a normal or near-normal left ventricular ejection fraction (LVEF). Such patients share similar signs and symptoms as patients who have heart failure and a reduced LVEF, as well as an impaired quality of life and a poor prognosis. However at the time of TOPCAT, the benefit of medical therapies for heart failure was limited to those with a reduced LVEF. Due to a lack of favorable evidence from clinical trials, clinical guidelines offered no specific recommendations for the management of heart failure in patients with preserved LVEF except for attention to coexisting conditions.
Among patients with heart failure and a reduced LVEF and those with myocardial infarction complicated by heart failure and left ventricular dysfunction, mineralocorticoid receptor antagonists have been shown to be effective in reducing overall mortality and hospitalizations for heart failure. In small mechanistic studies involving patients with heart failure and preserved left ventricular function, mineralocorticoid receptor antagonists improved measures of diastolic function. However, rigorous testing was needed regarding their effect on clinical outcomes in patients with preserved LVEF. Therefore, the TOPCAT trial was initiated to determine whether treatment with spironolactone, an aldosterone antagonist, would improve clinical outcomes in patients with symptomatic heart failure and a relatively preserved LVEF.
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Participants
Patients 50 years of age or older were eligible if they had at least one sign and at least one symptom of heart failure on a pre-specified list of clinically defined signs and symptoms, a LVEF ≥ 45%, controlled systolic blood pressure (< 140 mm Hg or 140-160 mm Hg if subject was being treated with 3 or more medications), and a serum potassium level of less than 5.0 mmol per liter. In addition, eligible patients were stratified by two eligibility categories: (1) history of hospitalization within the previous 12 months, with management of heart failure a major component of the care provided, or (2) elevated brain natriuretic peptide (BNP) level within 60 days before randomization.
Exclusion criteria included severe systemic illness with a life expectancy of less than 3 years, severe renal dysfunction, and specific coexisting conditions, medications, or acute events.
A total of 3445 participants were enrolled, with 1722 assigned to the spironolactone group and 1723 assigned to the placebo group. Among these, 2464 participants were enrolled via the hospitalization stratum and 981 were enrolled via the BNP stratum.
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Design
TOPCAT was a phase 3, multicenter, international, randomized, double-blind, and placebo controlled trial. Eligible participants were randomly assigned to receive either spironolactone or placebo in a 1:1 ratio. Randomization was stratified according to whether the patient met the criterion for previous hospitalization or BNP elevation. The baseline visit included assessment of socio-demographics, physical characteristics, medical history, lifestyle factors, laboratory measures, electrocardiography variables and health-related quality of life and functional status.
Study drugs were initially administered at a dose of 15 mg once daily, which was increased as tolerated to a maximum of 45 mg daily during the first four months after randomization. Subsequent dose adjustments were made as required and subjects continued to receive other treatments for heart failure and co-existing illnesses. Measurement of potassium and creatinine levels was required within 1 week after a change in the study-drug dose and at each scheduled study visit. Follow-up visits to monitor symptoms, medications, and events and to dispense study drug were scheduled every four months during the subject’s first year on the study, and every six months thereafter. The mean follow-up interval was 3.3 years in each study group. Repository blood and urine samples were collected at the baseline and 1 year visits from consenting subjects.
The primary endpoint was a composite of cardiovascular mortality, aborted cardiac arrest or hospitalization for the management of heart failure. Secondary endpoints included all-cause mortality, hospitalization for heart failure management, new onset of diabetes mellitus or atrial fibrillation, and quality of life.
A subset of subjects also participated in the Echocardiography or Echocardiography and Vascular Stiffness ancillary studies. Echocardiography, and additionally tonometry in the Echocardiography and Vascular Stiffness study, were performed at baseline and at either 12 or 18 months following randomization. If the subject was already enrolled in the TOPCAT trial at the time the ancillary study was initiated, but had not yet reached the 18 month visit, baseline was determined via a retrospective analysis performed on any echocardiographic images completed within 60 days prior to TOPCAT enrollment and no tonometry was performed if applicable.
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Conclusions
In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. However, the drug reduced the secondary endpoint of heart failure hospitalization incidence.
N Engl J Med. 2014 Apr 10;370(15):1383-92.
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Disease classification
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Publications
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Mat typesBuffy Coat
DNA
Plasma
Serum
Urine
Whole Blood
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Network
The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.
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Subjects
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Age
Spironolactone Placebo All N % N % N % 50 to 54 129 7.49 139 8.07 268 7.78 55 to 59 205 11.90 223 12.94 428 12.42 60 to 64 297 17.25 270 15.67 567 16.46 65 to 69 281 16.32 284 16.48 565 16.40 70 to 74 290 16.84 326 18.92 616 17.88 75 to 79 258 14.98 240 13.93 498 14.46 80 to 84 175 10.16 156 9.05 331 9.61 85 to 90 87 5.05 85 4.93 172 4.99
Last Modified: March 12, 2025, 11:36 a.m. -
Sex
Spironolactone Placebo All N % N % N % 1:Male 834 48.43 836 48.52 1670 48.48 2:Female 888 51.57 887 51.48 1775 51.52
Last Modified: March 12, 2025, 11:36 a.m. -
Race
Spironolactone Placebo All N % N % N % 1: White 1525 88.56 1537 89.20 3062 88.88 2: Black 153 8.89 149 8.65 302 8.77 3: Other 44 2.56 37 2.15 81 2.35
Last Modified: March 12, 2025, 11:36 a.m.
Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request.
Section 3.0 of the BioLINCC Handbook
describes the components of the review process.
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Material Types
Last Modified: Aug. 18, 2016, 3:44 p.m. -
General Freeze/Thaw Status
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Visits (Vials)
12 March 2025
Serum
Plasma
Whole Blood
DNA
Buffy Coat
Urine
Total
Baseline
1,356
741
35
1,697
30
2,366
6,225
Month 4
3
1
0
2
1
3
10
Month 12
1,421
591
83
1,286
32
1,977
5,390
Last Modified: March 12, 2025, 11:36 a.m. -
Visits (Subjects)
12 March 2025
Serum
Total number of subjects
Average volume (ml) per subject
Baseline
442
1.39
Month 4
1
3.70
Month 12
365
2.41
Plasma
Total number of subjects
Average volume (ml) per subject
Baseline
406
0.45
Month 4
1
2.30
Month 12
339
0.56
Whole Blood
Total number of subjects
Average volume (ml) per subject
Baseline
35
1.43
Month 12
83
1.48
Buffy Coat
Total number of subjects
Average vials per subject
Baseline
30
1.00
Month 4
1
1.00
Month 12
32
1.00
Urine
Total number of subjects
Average volume (ml) per subject
Baseline
436
8.00
Month 4
1
14.80
Month 12
351
8.14
DNA
Total number of subjects
Average mass (µg) per subject
Average vials per subject
Baseline
394
24.09
4.31
Month 4
1
1.63
2.00
Month 12
313
38.06
4.11
Last Modified: March 12, 2025, 11:36 a.m.