Phase 4 N=53 Randomized Quadruple-blind Treatment

Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy

Myocardial Fibrosis · Hypertrophic Cardiomyopathy

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View on ClinicalTrials.gov: NCT00879060 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Apr 2021

Primary outcome: Primary: Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. — 2.1; 2.1; 0.7; 0.6 micrograms/L — p=1.0

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Spironolactone (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Tufts Medical Center
Primary completion: Nov 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.	2.1; 2.1; 0.7; 0.6; 4.7; 4.5	1.0
SECONDARY Measure of Functional Capacity: Peak Oxygen Consumption With Exercise	30; 28; 29; 29	0.7
SECONDARY Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class	1.6; 1.5; 1.7; 1.6	0.8
SECONDARY Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e')	14; 15; 13; 13	1.0
SECONDARY Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV)	1.1; 2.5; 1.8; 2.8	0.7
SECONDARY Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm)	22; 21; 22; 19	0.4
SECONDARY Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2)	133; 145; 129; 146	0.7
SECONDARY Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm)	40; 41; 40; 40	0.8

Summary

Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiomyopathy and remains the leading cause of sudden cardiac death in young people and an important cause of heart failure symptoms and death at any age. In HCM, pathological remodeling of the left ventricle involving myocardial fibrosis is likely a major contributor to cardiac dysfunction and also a nidus for the generation of ventricular arrhythmias. Serum markers of collagen turnover have been shown to reliably reflect the magnitude of myocardial fibrosis in a variety of cardiovascular diseases. In addition, aldosterone antagonist drugs have been shown to decrease fibrous tissue formation in the myocardium in certain pathologic cardiovascular states in which aldosterone production is increased. In HCM, aldosterone production is up-regulated and has been implicated in the formation of myocardial fibrosis. Therefore, the specific aims of this proposal are to: 1. assess serum markers of collagen turnover at baseline and correlate these findings with a variety of clinical and morphologic disease parameters 2. examine the effects of a 12-month treatment with the aldosterone antagonist spironolactone on magnitude of fibrosis as measured by serum markers of collagen turnover as well as changes in clinical and morphologic disease parameters. 3. explore the effects of a 12-month treatment with aldosterone antagonist spironolactone on heart failure status, diastolic function, arrhythmic burden, and total LV mass and quantity of fibrosis by CMR. The results of this proposal will offer important insights into the clinical significance of myocardial fibrosis in this primary genetic cardiomyopathy. The demonstration that spironolactone decreases fibrosis and improves clinical course would provide the rational for a larger multicenter clinical trial evaluating this novel therapy for improving clinical outcome in patients with HCM.

Eligibility Criteria

Inclusion Criteria

Hypertrophic cardiomyopathy
Able to swallow pills
No prior septal reduction therapy
Negative serum or hCG pregnancy test

Exclusion Criteria

Unable or unwilling to perform treadmill cardiopulmonary exercise test
Prior surgical myectomy or alcohol septal ablation
Known or suspected infiltrative or glycogen storage disease
Significant coronary artery disease, defined as atherosclerotic coronary artery narrowing >70% of the luminal diameter by coronary angiography
Severe obstructive pulmonary disease, defined as forced expiratory volume in 1 second (FEV1) 5.0 mmol/L.
Calculated creatinine clearance <30 ml/min using Cockcroft-Gault formula.
Pregnant or breast feeding
Poorly controlled systemic hypertension, defined as systolic blood pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, during 2 clinic visits.
Known conditions associated with elevated serum concentrations of PIIINP (e.g., chronic liver disease, diabetes mellitus, tumors, pulmonary fibrosis, bone and rheumatoid diseases, extensive wounds) or PINP (e.g., alcoholic liver disease, metabolic bone disease, thyroid disorders), including recent trauma (≤2 weeks) or surgery (≤6 months)
Taking drugs known to directly influence collagen metabolism including, amiodorone, ACE or angiotensin II inhibitors, aldosterone antagonists, statins, glucocorticoids and estrogens
Patients with ICDs/pacemakers will be recruited in the study, but will be excluded from the CMR component.

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Data sourced from ClinicalTrials.gov (NCT00879060). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.