TOPCAT is
a multi-center, international, randomized, double blind placebo-controlled
trial of the aldosterone antagonist spironolactone, in 3515
adults with heart failure and left ventricular ejection fraction
of at least 45%, recruited from over 200 clinical centers.
The trial is sponsored by the National Heart, Lung, and Blood
Institute of the National Institutes of Health.
ENDPOINTS
The primary endpoint is a composite of cardiovascular
mortality, aborted cardiac arrest or hospitalization for the
management of heart failure. Secondary endpoints include
all-cause mortality, new onset of diabetes mellitus or atrial
fibrillation, and quality of life.
TRIAL DESIGN
The trial duration is approximately 6 years, with approximately 4 years for subject
enrollment and an additional 2 years of follow-up, allowing
for an average subject follow-up of 3.45 years. An echocardiogram
reflecting ejection fraction > 45% will determine
study eligibility. The trial will have 90% power to detect
a relative reduction of 20% in the primary endpoint.
ELIGIBILITY
The study population will include those who meet the inclusion
criteria, some of which are:
Male or female
age 50 years or older;
Heart failure
with preserved systolic function (determined by signs and
symptoms in conjunction with prior hospital admission and/or
brain natriuretic peptide (BNP) level);
Left ventricular
ejection fraction > 45% (per local reading);
Controlled
systolic blood pressure (SBP);
Serum potassium
< 5.0 mmol/L.
TREATMENT
Study drug dosing will start at 15 mg/day and may be titrated
up to 45 mg according to subject tolerance, safety parameters,
and symptoms, and will be continued throughout the trial.
Following each change in the dosing regimen, subjects will
have blood drawn for safety labs 1 week later. Subjects will
take study medication every day according to specific instructions.
All other treatments will follow accepted local standards
for medical care for specific morbidities as described by
the American College of Cardiology (ACC), the American Heart
Association (AHA), and the European Society of Cardiology
(ESC) Practice Guidelines, as appropriate. Such treatments
may also be adjusted by the local medical practitioner, if
necessary. All randomized subjects will be followed even if
study drug is discontinued ahead of schedule, except in the
case that the subject refuses to participate further in the
study.
