Hypertrophic cardiomyopathy MedDRA version: 19.0 Level: LLT Classification code 10020204 Term: HOCM Hypertrophic obstructive cardiomyopathy System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Diovan 40 mg
Pharmaceutical Form: Coated tablet
INN or Proposed INN: VALSARTAN
CAS Number: 137862-53-4
Current Sponsor code: Diovan
Other descriptive name: Diovan
Concentration unit: mg mi
Sponsors
National Heart, Lung, and Blood Institute / National Institutes of Health
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 5.2 Inclusion Criteria 1. All subjects must have a Pathogenic or Likely Pathogenic HCM Sarcomere Mutation a. The following categories of mutations are considered acceptable for subjects who have previously undergone clinical genetic testing. If results are ambiguous or testing was performed at a lab other than those listed below, they will be reviewed by the Clinical Coordinating Center to determine eligibility. i. Laboratory for Molecular Medicine 1. Pathogenic 2. Likely Pathogenic ii. Transgenomics/ PGXHealth 1. Class I iii. GeneDx 1. Disease causing 2. Variant, likely disease-causing 3. Published, disease-causing mutation 4. Novel, likely disease-causing, mutation iv. Correlagen 1. Associated 2. Probably Associated 2. Group 1 Cohort a. LV wall thickness =12 mm and =25 mm or z score =3 and =18 as determined by rapid assessment by the echocardiographic core laboratory b. NYHA functional class I or II; no perceived or only slight limitations in physical activities c. No resting or provokable LV obstruction (peak gradient = 30 mmHg) on clinically-obtained ETT-echo within the past 24 months or transthoracic echo with Valsalva maneuver within the past 12 months d. Age 8-45 years 3. Group 2 Cohort (G+/LVH-) a. LV Wall Thickness =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 5.3 Subject Exclusion Criteria 1. Contraindication to ARB administration, including impaired renal function, hyperkalemia (serum K>5.0 mmol/L), prior history of angioedema 2. Medical conditions associated with increased collagen turnover that may confound interpretation of biomarkers of collagen synthesis (liver, pulmonary or renal fibrosis, inflammatory states, cancer, trauma or surgery within 6 months of enrollment) 3. Concomitant use of Spironolactone, Lithium, Aliskren, ARB or ACE-inhibitors.. If these drugs are in active use but not necessary for medical care, they may be discontinued and baseline studies can be performed after a 2-week washout period. 4. Pregnant or breastfeeding females 5. Females of childbearing potential with no effective contraceptive method (including abstinence) 6. Uncontrolled systemic HTN [persistent SBP>160 and/or DBP>90 in adult or equivalent in children (e.g. SBP>99th or DBP>95th percentile for sex, age, and height centile based on the American Academy of Pediatrics normal values) 7. Obstructive physiology, defined by resting, Valsalva-provoked or exercise-induced gradient >30mmHg within the past 24 months 8. Prior septal myectomy or alcohol septal ablation 9. Known, suspected, or symptomatic coronary artery disease or evidence of prior myocardial infarction based on symptoms or cardiac imaging 10. More than mild valvular heart disease or clinically significant congenital heart disease. Allowable conditions include bicuspid aortic valve without clinically significant stenosis or regurgitation; spontaneously closed ventricular septal defects; patent foramen ovale, small (= 2 mm) restrictive ventricular septal defects with normal ventricular size, and other minor defects that are considered allowable after [review and consensus by participating pediatric cardiologists, overall study PI and] adjudication by the echocardiographic core laboratory. 11. LVEF <55% 12. Concomitant medical conditions that would preclude performance of or confound interpretation of echocardiography, exercise testing, or CMR (e.g., renal insufficiency, lung disease, orthopedic/rheumatologic conditions, atrial fibrillation) 13. Secondary prevention implantable cardioverter-defibrillator device (ICD; primary prevention ICDs without a history of appropriate therapy, including shock or ATP, are allowable). 14. Prior treatment or hospitalization for symptomatic heart failure 15. Participation in a clinical trial (except observational studies) involving investigational medications within the previous 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of Valsartan in young patients in an early stage of hypertrophic cardiomyopathy.;Secondary Objective: To assess the safety of Valsartan in young patients in an early stage of hypertrophic cardiomyopathy.;Primary end point(s): We hypothesize that administration of the ARB, valsartan, compared to placebo, will demonstrate treatment efficacy across multiple domains of cardiac structure/ function and clinical outcomes. Average z scores will be calculated for key components of the primary outcome. The primary endpoint will compare the composite total z score across all domains for sarcomere mutation carriers with at least borderline left ventricular hypertrophy (designated Group 1) treated with valsartan compared to placebo. ;Timepoint(s) of evaluation of this end point: 1 year and 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): We will more broadly characterize the impact of valsartan treatment on disease pathology, and identify variables that may influence both treatment response and disease progression. We will assess the impact of valsartan therapy on the important but relatively rare cohort of preclinical HCM (designated Group 2). These analyses will provide a crucial foundation for future studies to test novel strategies of disease prevention. ;Timepoint(s) of evaluation of this end point: 1 year and 2 years | — |
Countries
Denmark
Contacts
Public ContactKristin Burns
Heart Development and Structural Diseases Branch / Division of Cardiovascular Sciences National Heart, Lung, and Blood I
Outcome results
None listed