Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) - Catalog

Name

Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT)

Accession Number

HLB01341616a

Acronym

TOPCAT

Related studies

BSI Study IDs

TCT

Is public use dataset

False

Keywords

Has Study Datasets

True

Has Specimens

True

Specimen ID Type

Coded

Study Website

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

Study type

Clinical Trial

Collection Type

Open BioLINCC Study

Cohort type

Adult

Interventions

Drug: SpironolactoneDrug: Placebo

Study Open Date (Data)

2016-04-13

Study Open Date (Specimens)

2016-04-13

Date materials available

2011-08-04

Last updated

2016-04-12

Study period

August 2006 – June 2013

Study Contacts
NHLBI Division

DCVS

Classification

Heart

HIV study classification

non-HIV

COVID study classification

non-COVID

Pre-Website # of Specimens Shipped

0

# of Returned Specimens

0

Conditions

Cardiovascular Diseases
Heart Diseases
Heart Failure, Congestive

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.

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.

Subjects

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.

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.

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.

Disease classification

Publications

Mat types

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.

  • Subjects
  • 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: April 28, 2016, 4:10 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: April 28, 2016, 4:10 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: April 28, 2016, 4:10 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 of the BioLINCC handbook describes the components of the review process

  • Material Types

    Last Modified: Aug. 18, 2016, 3:44 p.m.
  • General Freeze/Thaw Status
  • 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: June 14, 2023, 4:53 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