Hypertrophic Cardiomyopathy
Conditions
Keywords
Hypertrophic nonobstructive cardiomyopathy
Brief summary
The purpose of this study is to determine whether taking losartan helps people with hypertrophic nonobstructive cardiomyopathy feel better by decreasing the amount of heart muscle thickening and/or the amount of heart muscle scarring.
Detailed description
Hypertrophic cardiomyopathy (HCM) is characterized by idiopathic cardiac hypertrophy, heart failure, ischemia even in the absence of epicardial coronary artery disease, and arrhythmias. The pathological features of HCM include hypertrophy and disarray, interstitial fibrosis, and increased arteriolar wall thickness. Hypertrophy and fibrosis are major determinants of morbidity and mortality in hypertrophic cardiomyopathy. Some investigators have demonstrated that interstitial fibrosis and hypertrophy occur secondarily, in response to trophic and mitotic factors in the heart. Therefore, blocking trophic factors may attenuate or potentially reverse hypertrophy and fibrosis in HCM. Angiotensin II has trophic and profibrotic effects on the heart, and blockade of angiotensin II type I receptors has been shown to attenuate myocardial hypertrophy and fibrosis in acquired cardiac disease in humans and animal models. We hypothesize that treatment with the selective angiotensin II type receptor antagonist, losartan, will decrease both hypertrophy and fibrosis, improve diastolic function, reduce symptoms, and improve functional status in patients with HCM.
Interventions
DRUGlosartan
Losartan 50 mg b.i.d
DRUGplacebo
Placebo b.i.d.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with hypertrophic cardiomyopathy * Left ventricular outflow tract (LVOT) gradient less than 30 mm Hg at rest * Age 18 years or older
Exclusion criteria
* Contraindication to losartan * Already taking losartan * Contraindication to MRI * Hemodynamic instability
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage Change From Baseline in Extent of Left Ventricular Fibrosis at 1 Year as Assessed by Magnetic Resonance Imaging. | Baseline and 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Percentage Change From Baseline in Left Ventricular Mass at 1 Year as Assessed by Magnetic Resonance Imaging. | Baseline and 1 year |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment 4-07 through 3-10.
Participants by arm
| Arm | Count |
|---|---|
| Losartan 50 mg PO BID | 11 |
| Placebo | 9 |
| Total | 20 |
Baseline characteristics
| Characteristic | Placebo | Losartan 50 mg PO BID | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 19 Participants |
| Age Continuous | 54 years STANDARD_DEVIATION 11 | 49 years STANDARD_DEVIATION 14 | 51 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 9 participants | 11 participants | 20 participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 9 |
| serious Total, serious adverse events | 0 / 11 | 0 / 9 |
Outcome results
Primary
Percentage Change From Baseline in Extent of Left Ventricular Fibrosis at 1 Year as Assessed by Magnetic Resonance Imaging.
Time frame: Baseline and 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg PO BID | Percentage Change From Baseline in Extent of Left Ventricular Fibrosis at 1 Year as Assessed by Magnetic Resonance Imaging. | -23 Percentage change in fibrotic myocardium | Standard Deviation 45 |
| Placebo | Percentage Change From Baseline in Extent of Left Ventricular Fibrosis at 1 Year as Assessed by Magnetic Resonance Imaging. | 31 Percentage change in fibrotic myocardium | Standard Deviation 26 |
Comparison: Mann-Whitney-Wilcoxon testp-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
Percentage Change From Baseline in Left Ventricular Mass at 1 Year as Assessed by Magnetic Resonance Imaging.
Time frame: Baseline and 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Losartan 50 mg PO BID | Percentage Change From Baseline in Left Ventricular Mass at 1 Year as Assessed by Magnetic Resonance Imaging. | -5 Percentage change in LV mass | Inter-Quartile Range 11 |
| Placebo | Percentage Change From Baseline in Left Ventricular Mass at 1 Year as Assessed by Magnetic Resonance Imaging. | 5 Percentage change in LV mass | Inter-Quartile Range 28 |
Comparison: Mann-Whitney-Wilcoxon testp-value: 0.06Wilcoxon (Mann-Whitney)