Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy

May 3, 2018 updated by: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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 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.

Study Type

Interventional

Enrollment (Anticipated)

260

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200092
        • Xinhua Hospital, Shanghai Jiao Tong University School of Medicne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: control
The participants in control group do not take spironolactone.
Experimental: spironolactone
The participants in spironolactone group take 10-20mg spironolactone orally and daily.
Drug: Spironolactone
The participants in this arm will be prescribed to take 20mg spironolactone orally and daily. Serum potassium concentration and creatinine and blood pressure will be monitored regularly to make the participants safe.
Other Names:
  • LuoNeiZhi

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the extent of late gadolinium enhancement (LGE+%)
Time Frame: 2 years
LGE-CMR will be used to measure the extent of LV fibrosis in the participants. 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).
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Collaborators

RenJi Hospital
Ruijin Hospital
Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Investigators

  • Principal Investigator: Yi-Gang Li, MD, Xinhua Hospital, Shanghai Jiao Tong University School of Medcine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

May 14, 2018

Primary Completion (Anticipated)

October 1, 2019

Study Completion (Anticipated)

July 1, 2020

Study Registration Dates

First Submitted

October 27, 2016

First Submitted That Met QC Criteria

October 27, 2016

First Posted (Estimate)

October 31, 2016

Study Record Updates

Last Update Posted (Actual)

May 9, 2018

Last Update Submitted That Met QC Criteria

May 3, 2018

Last Verified

October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XH-16-032

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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