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Trial record 1 of 4 for:    TOPCAT
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Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function (TOPCAT)

This study has been completed.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
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 
Overall Participants Analyzed 
[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 by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: New England Research Institutes
ClinicalTrials.gov Identifier: NCT00094302     History of Changes
Other Study ID Numbers: 160
HHSN268200425207C ( Other Grant/Funding Number: NIH contract )
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