Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function (TOPCAT)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New England Research Institutes
ClinicalTrials.gov Identifier:
NCT00094302
First received: October 15, 2004
Last updated: February 11, 2015
Last verified: January 2014
Results First Received: December 1, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Conditions: Cardiovascular Diseases
Heart Diseases
Heart Failure, Congestive
Interventions: Drug: Spironolactone
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
TOPCAT enrolled 3445 patients with heart failure and preserved ejection fraction at 233 academic and community medical centers in 6 countries between August 2006 and January 2012. Trial follow-up ended in June 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Trial randomization was stratified by whether patients were enrolled into the study on the basis of having a hospitalization for heart failure within the past year (N=2,464) or having an elevated natriuretic peptide level within 60 days before randomization (N=981). The second criterion was considered only for those who did not meet the first.

Reporting Groups
  Description
Placebo Placebo of spironolactone
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.

Participant Flow:   Overall Study
    Placebo     Spironolactone  
STARTED     1723     1722  
COMPLETED     1306     1316  
NOT COMPLETED     417     406  
Lost to Follow-up                 43                 41  
Physician Decision                 5                 8  
Withdrawal by Subject                 103                 111  
Death                 266                 246  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Placebo of spironolactone
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.
Total Total of all reporting groups

Baseline Measures
    Placebo     Spironolactone     Total  
Number of Participants  
[units: participants]
  1723     1722     3445  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     649     654     1303  
>=65 years     1074     1068     2142  
Age  
[units: years]
Median (Inter-Quartile Range)
  68.7    (60.7 to 75.5)     68.7    (61.0 to 76.4)     68.7    (60.9 to 75.9)  
Gender  
[units: participants]
     
Female     887     888     1775  
Male     836     834     1670  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     3     6     9  
Asian     9     10     19  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     149     151     300  
White     1537     1525     3062  
More than one race     0     2     2  
Unknown or Not Reported     25     28     53  
Region of Enrollment  
[units: participants]
     
United States     579     572     1151  
Canada     160     166     326  
Argentina     60     63     123  
Brazil     82     85     167  
Russian Federation     537     529     1066  
Georgia     305     307     612  
Eligibility Stratum [1]
[units: participants]
     
Hospitalization in previous year for heart failure     1232     1232     2464  
Elevated natriuretic peptide in previous 60 days     491     490     981  
[1] Eligible patients were assigned to one of two strata before randomization, according to whether they had at least one hospitalization within the previous 12 months in which management of heart failure was a major component of the care provided, or in absence of that criterion, an elevated brain natriuretic peptide (BNP) level within 60 days prior to randomization (a brain natriuretic peptide [BNP] level ≥100 pg per milliliter or an N-terminal pro-BNP [NTproBNP] level ≥360 pg per milliliter).



  Outcome Measures
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1.  Primary:   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. ]

2.  Secondary:   Cardiovascular Mortality   [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]

3.  Secondary:   Aborted Cardiac Arrest   [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]

4.  Secondary:   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. ]

5.  Secondary:   All-cause Mortality   [ Time Frame: Randomization through each subject’s last semi-annual visit, up to a maximum of 6 years per subject. ]

6.  Secondary:   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. ]

7.  Secondary:   Cardiovascular-related Hospitalization   [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]

8.  Secondary:   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. ]

9.  Secondary:   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. ]

10.  Secondary:   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. ]

11.  Secondary:   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. ]

12.  Secondary:   Myocardial Infarction   [ Time Frame: Randomization through each subject’s last semi-annual visit, up to a maximum of 6 years per subject. ]

13.  Secondary:   Stroke   [ Time Frame: Randomization through each subject’s last semi-annual visit, up to a maximum of 6 years per subject. ]

14.  Secondary:   Deterioration of Renal Function   [ Time Frame: Randomization through each subject’s last semi-annual visit, up to a maximum of 6 years per subject. ]

15.  Secondary:   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. ]

16.  Secondary:   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. ]

17.  Secondary:   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. ]

18.  Secondary:   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. ]

19.  Secondary:   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. ]

20.  Secondary:   Hospitalization for Any Reason   [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]

21.  Secondary:   Potassium   [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]

22.  Secondary:   Serum Creatinine   [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]

23.  Secondary:   Sodium   [ Time Frame: Randomization through each subject’s last semi-annual visit, up to a maximum of 6 years per subject. ]

24.  Secondary:   Chloride   [ Time Frame: Randomization through each subject's last semi-annual visit, up to a maximum of 6 years per subject. ]

25.  Secondary:   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. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Brian Harty
Organization: New England Research Institutes
phone: 617-972-3224
e-mail: bharty@neriscience.com


Publications of Results:

Other Publications:
Publications automatically indexed to this study:

Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00094302     History of Changes
Other Study ID Numbers: 160, HHSN268200425207C
Study First Received: October 15, 2004
Results First Received: December 1, 2014
Last Updated: February 11, 2015
Health Authority: United States: Food and Drug Administration