An international study of the effect of Valsartan in hypertrophic cardiomyopathy.

Phase 1

• Conditions: Hypertrophic cardiomyopathy; MedDRA version: 19.0Level: LLTClassification code 10020204Term: HOCM Hypertrophic obstructive cardiomyopathySystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-002283-16-DK
• Lead Sponsor: ational Heart, Lung, and Blood Institute / National Institutes of Health

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-12-16
• Last Update Posted: 18 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

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 <12 mm and z score <3, as determined by rapid assessment by the echocardiographic core laboratory
b.Age 10-25 years
c.E’ z score = -1.5 OR ECG abnormalities other than NSSTW changes (Q waves, T wave inversion, repolarization changes) OR LV wall thickness z-score 1.5-2.9 combined with LV thickness to dimension ratio =0.19 (as determined by rapid assessment by the echocardiographic core laboratory)

4.Able to attend follow-up appointments, complete all study assessments, and provide written informed consent

Are the trial subjects under 18? yes
Number of subjects for this age range: 75
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

5.3Subject 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified