Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy

• Status: Unknown status
• Trial end date: 2020-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Collaborators: RenJi Hospital; Ruijin Hospital; Shanghai Jiao Tong University Affiliated Sixth People's Hospital
• Treatments: Spironolactone

Criteria

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 any imaging technique (echocardiography, cardiac magnetic resonance imaging (CMR) or computed 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 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 the trial

• 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 is obligatory 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 serum potassium ≥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 alanine aminotransferase levels > 3 times the upper limit of normal as read at the local laboratory

• women of child-bearing or lactation

• cancer