Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy

Phase

Condition

Congestive Heart Failure

Circulation Disorders

Heart Defect

Treatment

N/A

Clinical Study ID

NCT02948998

XH-16-032

Ages 18-75
All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

male or female, aged from 18 to 75 years
a wall thickness ≥15mm in one or more LV myocardial segments -- as measured by anyimaging technique (echocardiography, cardiac magnetic resonance imaging (CMR) orcomputed tomography (CT) --that is not explained solely by loading conditions
LVEF≥50%
serum potassium ＜5.0mmol/L
systolic blood pressure ≥100mmHg
not taking spironolactone for the last 6 months
willing to comply with scheduled visits
informed consent form signed by the subject before participation in the trial

Exclusion

Exclusion Criteria:

cardiac magnetic resonance imaging (CMR) can not be accepted
spironolactone is not tolerant or is contradicted
taking spironolactone during the last 6 months
severe systemic illness with life expectancy judged ＜ 3 years
expected to have ventricular septal myectomy or septal alcohol ablation during thetrial
expected to have valve repair or replacement during the trial
history of myocardial infarction
angiotension-converting-enzyme inhibitor (ACE-I) or AT-1 receptor blockade isobligatory because of any reason
systolic blood pressure ＜90mmHg
known orthostatic hypotension
history of hyperkalemia (serum potassium ≥5.5mmol/L) in the past 6 months or serumpotassium ≥5.0mmol/L within the past 2 weeks
severe renal dysfunction, defined as an eGFR ＜30mL/min or serum creatinine ≥221mmol/L
hemodialysis
known chronic hepatic disease, defined as aspartate aminotransferase and alanineaminotransferase levels ＞ 3 times the upper limit of normal as read at the locallaboratory
women of child-bearing or lactation
cancer

Study Design

May 14, 2018

July 31, 2020

Study Description

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 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.

Connect with a study center

Xinhua Hospital, Shanghai Jiao Tong University School of Medicne
Shanghai, Shanghai 200092
China
Site Not Available

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