Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) - Catalog
Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)
HLB01341624a
TOPCAT
TCT
False
True
True
Coded
False
Clinical Trial
Open BioLINCC Study
Adult
Drug: SpironolactoneDrug: Placebo
2016-04-13
2016-04-13
2011-08-04
2016-04-12
August 2006 – June 2013
DCVS
Heart
non-HIV
non-COVID
0
0
No
No
No
No
Yes, For Some Specimens
Yes
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.
Cardiovascular Diseases
Heart Diseases
Heart Failure, Congestive
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.
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.
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.
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.
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.
Buffy Coat
DNA
Plasma
Serum
Urine
Whole Blood
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: Aug. 28, 2024, 4:07 p.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: Aug. 28, 2024, 4:07 p.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: Aug. 28, 2024, 4:07 p.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)
06/14/2023
Serum Plasma Whole Blood DNA Buffy Coat Urine Total Baseline 1,753 1,114 51 1,623 48 2,506 7,095 Month 4 3 1 0 2 1 3 10 Month 12 1,682 915 130 535 180 1,977 5,419
Last Modified: Aug. 28, 2024, 4:07 p.m. -
Visits (Subjects)
06/14/2023
Serum Total number of subjects Average volume (ml) per subject Baseline 442 2.12 Month 4 1 3.70 Month 12 365 3.13 Plasma Total number of subjects Average volume (ml) per subject Baseline 434 0.67 Month 4 1 2.30 Month 12 363 0.77 Whole Blood Total number of subjects Average volume (ml) per subject Baseline 51 1.50 Month 12 130 1.54 Buffy Coat Total number of subjects Average vials per subject Baseline 48 1.00 Month 4 1 1.00 Month 12 180 1.00 Urine Total number of subjects Average volume (ml) per subject Baseline 436 8.25 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 398 18.95 4.08 Month 4 1 1.63 2.00 Month 12 180 6.68 2.97
Last Modified: Aug. 28, 2024, 4:07 p.m.