Hypertrophic Cardiomyopathy Clinical Trial
Official title:
Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy-- a Multicenter Randomized Control Trial
Hypertrophic Cardiomyopathy (HCM) is the most common hereditary heart disease with high
mortality. Heart failure is the most common complication (about 50% incidence) in these
patients. However, it is lack of efficiency medicine to treat heart failure for HCM patients.
Recent studies found fibrosis was common in HCM patients and it was progressive with aging.
Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is a gold standard to
measure the left ventricular(LV) fibrosis extent and been proven to be useful in HCM
patients.
Aldosterone plays an important role in the development of fibrosis. Meanwhile, a few studies
suggested that aldosterone might participate the development of fibrosis in HCM patients.
Spironolactone, a mineralocorticoid receptor antagonist, has been proven its effect on
inceasing the survival of the heart-failure patients with the eject fraction lower than 35%.
Thus, the investigators hypothesize that fibrosis is one important reason of heart failure
for HCM patients. The purpose of this study is to investigate whether small dosage and early
prescription of spironolactone to HCM patients can relieve and/or reverse the fibrosis
progress and improve patients' symptoms.
This study is a multicenter, randomized, controlled and open-label study being conducted in 4
centers in Shanghai, China. The primary objective of the study is to evaluate the efficacy of
spironolactone on relieving the LV fibrosis in HCM patients. This study plans to recruit 260
participants with definite HCM diagnosis. Then these participants will be randomized to two
groups-- "control group "(not taking spironolactone) and "spironolactone group" (taking 20mg
spironolactone orally and daily). LGE-CMR, echocardiography, 24-hour Holter,
electrocardiography (ECG), and blood test (including hemoglobin, creatitine, potassium, liver
enzymes, proBNP, TnT, angiotensin and aldosterone) will be performed before random allocation
and after 2 years. LGE-CMR will be used to measure the extent of fibrosis in LV. The extent
of LGE+% (the area showing LGE divided by the total area) before and after 2-year experiment
and the increase of LGE+% after 2-year experiment will be compared between control and
spironolactone groups. Meanwhile, symptoms, New York Heart Association classification of
cardiac function, arrhythmia, proBNP and TnT etc. will be compared between two groups.
Hypertrophic Cardiomyopathy (HCM) is the most common hereditary heart disease. Approximate
1--2% population of HCM patients die every year because of cardiocerebrovascular
complications in which heart failure, stroke and sudden cardiac deaths rank the top three.
Among them, heart failure has the highest incidence (about 50%) but the least ways to treat.
Even though the Heart Association of United States and Europe updated the guidelines for the
diagnosis and management of HCM, it is still lack of qualified clinical trials about medicine
for HCM in the real world.
Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is a gold standard to
measure the left ventricular(LV) fibrosis extent. Recent studies found that: (1)a proportion
of HCM patients have LV fibrosis during the early stage of disease; (2)the LV fibrosis in the
HCM patients is progressive; (3)about 91.5% population of HCM patients had late gadolinium
enhancement; and(4) late gadolinium enchancement in the HCM patients is related to the risk
of sudden death.
Fibrosis is an important pathology of heart failure for the patients with coronary artery
disease and dilated cardiomyopathy. The activation of renin-angiotensin-aldosterone system
plays a key role during the progression of heart failure. Small dosage of spironolactone has
been proven its effect on inceasing the survival of the heart-failure patients with the eject
fraction lower than 35%. Meanwhile, a few studies found aldosterone levels of LV myocytes
increased both in HCM patients and HCM transgenic mice. Furthermore, spironolactone, a
mineralocorticoid receptor antagonist, could reserve interstitial fibrosis, attenuate myocyte
disarray by 50%, and improve diastolic function in HCM transgenic mice.
Thus, the investigators hypothesize that fibrosis is one important reason of heart failure
for HCM patients and small dosage and early prescription of spironolactone to HCM patients
can relieve and/or reverse the fibrosis progress and improve patients' symptoms.
This study is a multicenter, randomized, controlled and open-label study being conducted in 4
centers in Shanghai, China. The primary objective of the study is to evaluate the efficacy of
spironolactone on relieving the LV fibrosis in HCM patients.
This study plans to recruit 260 participants with definite HCM diagnosis. Then these
participants will be randomized to two groups-- "control group "(not taking spironolactone)
and "spironolactone group" (taking 20mg spironolactone orally and daily). LGE-CMR,
echocardiography, 24-hour Holter, electrocardiography (ECG), and blood test (including
hemoglobin, creatitine, potassium, liver enzymes, proBNP, TnT, angiotensin and aldosterone)
will be performed before random allocation and after 2 years.
LGE-CMR will be used to measure the extent of fibrosis in LV. Myocardial areas showing signal
intensity ＞5 SD than mean signal intensity of normal myocardium were defined as segments with
LGE. LGE extent in each segment was expressed as the surface area showing LGE divided by the
total area of the given myocardial segment, and then summation of the planimetered LGE areas
in all short-axis slices yielded total LGE extent, which was subsequently expressed as a
proportion of total LV myocardium (LGE+%).
The extent of LGE+% before and after 2-year experiment and the increase of LGE+% after 2-year
experiment will be compared between control and spironolactone groups. Meanwhile, symptoms,
New York Heart Association classification of cardiac function, arrhythmia, proBNP and TnT
etc. will be compared between two groups.
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