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Hypertrophic CardiomyopathyPhase 2VANISHNCT01912534

Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM

A Phase 2 study testing Valsartan in people with Hypertrophic Cardiomyopathy, run by Carelon Research at 15 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this trial is to determine whether treatment with valsartan will have beneficial effect in early hypertrophic cardiomyopathy (HCM) by assessing many domains that reflect myocardial structure, function and biochemistry. Read more about this study

Who is it for?
Ages 8 to 45 years
Conditions the study is for
Hypertrophic Cardiomyopathy
What is being tested?
Valsartan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
211 participants
Where
15 sitesin 2 countries
Study dates
Mar 2014to Jul 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 1. All subjects must have a Pathogenic or Likely Pathogenic HCM Sarcomere Mutation
  • The following categories of mutations are considered acceptable for subjects who have previously undergone clinical genetic testing. If results are ambiguous, they will be reviewed by the Clinical Coordinating Center to determine eligibility.
  • Laboratory for Molecular Medicine (Pathogenic, Likely Pathogenic)
  • Transgenomics/ PGXHealth (Class I)
  • GeneDx (Disease causing; Variant; likely disease-causing; Published, disease-causing mutation; Novel, likely disease-causing, mutation)
  • Correlagen (Associated; Probably Associated)
Show all 32Show fewer
  • Group 1 (Overt HCM Cohort)
  • LV wall thickness ≥12 mm and ≤25 mm or z score ≥3 and ≤18 as determined by rapid assessment by the echocardiographic core laboratory
  • NYHA functional class I or II; no perceived or only slight limitations in physical activities
  • No resting or provokable LV obstruction (peak gradient ≤ 30 mmHg) on clinically-obtained Exercise Tolerance Test (ETT)-echo within the past 24 months or transthoracic echo with Valsalva maneuver within the past 12 months
  • Age 8-45 years
  • Able to attend follow-up appointments, complete all study assessments, and provide written informed consent
  • Group 2 (Preclinical HCM Cohort (G+/LVH-))
  • LV Wall Thickness <12 mm and z score <3 , as determined by rapid assessment by the echocardiographic core laboratory
  • Age 10-25 years
  • 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)
  • Able to attend follow-up appointments, complete all study assessments, and provide written informed consent
  • Subject Exclusion Criteria
  • Contraindication to angiotensin receptor blocker (ARB) administration, including impaired renal function, hyperkalemia (serum K>5.0 mmol/L), prior history of angioedema
  • 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)
  • Concomitant use of Spironolactone, Lithium, or Aliskiren, 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.
  • Pregnant or breastfeeding females - Females of childbearing potential with no effective contraceptive method (including abstinence)
  • 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)]
  • Obstructive physiology, defined by resting, Valsalva-provoked or exercise-induced gradient >30mmHg within the past 24 months
  • Prior septal myectomy or alcohol septal ablation
  • Known, suspected, or symptomatic coronary artery disease or evidence of prior myocardial infarction based on symptoms or cardiac imaging
  • 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.
  • Left ventricular ejection fraction (LVEF) <55%
  • 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)
  • Secondary prevention implantable cardioverter-defibrillator device (ICD; primary prevention ICDs without a history of appropriate therapy, including shock or ATP, are allowable).
  • Prior treatment or hospitalization for symptomatic heart failure
  • Participation in a clinical trial (except observational studies) involving investigational medications within the previous 30 days.

Who cannot join

None listed.

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States13 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • Children's Hospital Boston

    Boston, Massachusetts, 02115

  • University of Chicago

    Chicago, Illinois, 60637

  • Cinncinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Washington University School Medicine

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94305

Other trials in United States

Canada2 sites

  • Toronto General Hospital

    Toronto, Ontario, M4W3S5

  • Toronto Sick Kids

    Toronto, Ontario, M5G1X8

Other trials in Canada

About this study

The purpose of this trial is to determine whether treatment with valsartan will have beneficial effect in early hypertrophic cardiomyopathy (HCM) by assessing many domains that reflect myocardial structure, function and biochemistry.

Read the detailed description

This is a multicenter, double-blind, placebo-controlled Phase II, randomized clinical trial to assess the safety and efficacy of valsartan in attenuating disease evolution in early HCM. Sarcomere mutation carriers with asymptomatic or mildly symptomatic overt disease (NYHA class I-II), and mutation carriers without left ventricular hypertrophy (LVH) will be studied.

Being tested
Valsartan, Placebo
Keywords
Sarcomere Mutations
Medical subject headings
Cardiomyopathy, Hypertrophic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ValsartanDrug

    Also called Diovan

    40, 80 and 160 mg tablets of Valsartan

  • PlaceboDrug

    Also called Matching Placebo pills

    During Active Run-In, all patients take Valsartan. During maintenance, all patients are randomized to valsartan or placebo

Study groups in NCT01912534
Study groupRoleWhat they receive
ValsartanActive comparatorSubjects who tolerate active run-in and titration to target dose of valsartan will then undergo stratified randomization and begin blinded treatment with valsartan or matched placebo on maximal tolerated dose, according to their assigned treatment group. Treatment will continue for 2 years.
Receives: Drug: Valsartan; Drug: Placebo
PlaceboPlacebo comparatorSubjects who tolerate active run-in and titration to target dose of valsartan will then undergo stratified randomization and begin blinded treatment with valsartan or matched placebo on maximal tolerated dose, according to their assigned treatment group. Treatment will continue for 2 years.
Receives: Drug: Valsartan; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite z-score

    Composite z-score which is the average of 9 change-scores of: serum NTproBNP, serum high-sensitivity cardiac troponin, left ventricular (LV) mass, left atrial (LA) volume, LV end diastolic volume, LV end systolic volume, maximal LV wall thickness, echo E' velocity, echo S' velocity

    Measured: 2 years

Secondary outcomes (10)

  1. z-score serum NTproBNP

    Z-score for the 2 year change for serum NTproBNP

    Measured: 2 years

  2. z-score high sensitivity cardiac troponin

    Z-score for the 2 year change for high-sensitivity cardiac troponin

    Measured: 2 years

  3. z-score LV mass

    Z-score for the 2 year change in LV Mass

    Measured: 2 years

  4. z-score LA volume

    Z-score for the 2 year change in LA Volume

    Measured: 2 years

  5. z-score LV end diastolic volume

    Z-score for the 2 year change in LV end diastolic volume

    Measured: 2 years

  6. z-score LV end systolic volume

    Z-score for the 2 year change in LV end systolic volume

    Measured: 2 years

  7. z-score maximal LV wall thickness

    Z-score for the 2 year change in Maximal LV wall thickness

    Measured: 2 years

  8. z-score echo E' velocity

    Z-score for the 2 year change in echo E' velocity

    Measured: 2 years

  9. z-score echo S' velocity

    Z-score for the 2 year change in echo S' velocity

    Measured: 2 years

  10. Binary indicator of success or failure

    Success defined as an improvement at 2 years in any of the following: serum NTproBNP, serum high-sensitivity troponin, LV Mass, LA Volume, LV end diastolic volume, LV end systolic volume, Maximal LV wall thickness, echo E' velocity, or echo S' velocity

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2013 (estimated)
  2. Study startMar 2014
  3. Primary completionJul 2019
  4. Study completionJul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
211 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01912534
Sponsor's protocol ID
VANISH
Other IDs
5P50HL112349
Acronym
VANISH
Status last verified
Apr 2020
First submitted
5 Jun 2013
Last updated
11 Jan 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Ostrominski JW, Claggett BL, Jerosch-Herold M, Raja AA, Day SM, Russell MW, Zahka K, Pereira AC, Colan SD, Murphy AM, Canter C, Bach RG, Wheeler MT, Rossano JW, Owens AT, Mestroni L, Taylor MRG, Patel AR, Wilmot I, Soslow JH, Becker JR, Lakdawala NK, Bundgaard H, Vargas JD, Ho CY; Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) Investigators. Body Mass Index, Valsartan, and Myocardial Remodeling in Early-Stage Hypertrophic Cardiomyopathy: A Secondary Analysis of the Randomized VANISH Trial. J Am Heart Assoc. 2026 Oct 10:e050131. doi: 10.1161/JAHA.126.050131. Online ahead of print.

    PubMed 42858009

  • Topriceanu CC, Vissing CR, Axelsson Raja A, Day SM, Russell MW, Zahka K, Pereira AC, Colan SD, Murphy AM, Canter C, Bach RG, Wheeler MT, Rossano JW, Owens AT, Mestroni L, Taylor MRG, Moon JC, Captur G, Patel AR, Wilmot I, Soslow JH, Becker JR, Seidman CE, Lakdawala NK, Bundgaard H, Tahir UA, Ho CY. Proteomic Analysis of Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) Clinical Trial. Circ Heart Fail. 2025 Jun;18(6):e012393. doi: 10.1161/CIRCHEARTFAILURE.124.012393. Epub 2025 May 9.

    PubMed 40340372

  • Ostrominski JW, Claggett BL, Jerosch-Herold M, Raja AA, Day SM, Russell MW, Zahka K, Pereira AC, Colan SD, Murphy AM, Canter C, Bach RG, Wheeler MT, Rossano JW, Owens AT, Mestroni L, Taylor MRG, Patel AR, Wilmot I, Soslow JH, Becker JR, Lakdawala NK, Bundgaard H, Vargas JD, Ho CY; Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) Investigators. Valsartan and Cardiac Remodeling in Early-Stage Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial Cardiac Magnetic Resonance Substudy. JAMA Cardiol. 2025 Jun 1;10(6):617-623. doi: 10.1001/jamacardio.2024.5677.

    PubMed 40042824

  • Ireland CG, Burstein DS, Day SM, Axelsson Raja A, Russell MW, Zahka KG, Pereira A, Canter CE, Bach RG, Wheeler MT, Rossano JW, Owens AT, Bundgaard H, Mestroni L, Taylor MRG, Patel AR, Wilmot I, Soslow JH, Becker JR, Giverts I, Orav EJ, Claggett B, Lin KY, Ho CY. Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial. Circ Heart Fail. 2024 Aug;17(8):e011663. doi: 10.1161/CIRCHEARTFAILURE.124.011663. Epub 2024 Aug 1.

    PubMed 39087355

  • Vissing CR, Axelsson Raja A, Day SM, Russell MW, Zahka K, Lever HM, Pereira AC, Colan SD, Margossian R, Murphy AM, Canter C, Bach RG, Wheeler MT, Rossano JW, Owens AT, Benson L, Mestroni L, Taylor MRG, Patel AR, Wilmot I, Thrush P, Soslow JH, Becker JR, Seidman CE, Lakdawala NK, Cirino AL, McMurray JJV, MacRae CA, Solomon SD, Bundgaard H, Orav EJ, Ho CY; Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) Investigators. Cardiac Remodeling in Subclinical Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial. JAMA Cardiol. 2023 Nov 1;8(11):1083-1088. doi: 10.1001/jamacardio.2023.2808.

    PubMed 37672268

  • Ho CY, Day SM, Axelsson A, Russell MW, Zahka K, Lever HM, Pereira AC, Colan SD, Margossian R, Murphy AM, Canter C, Bach RG, Wheeler MT, Rossano JW, Owens AT, Bundgaard H, Benson L, Mestroni L, Taylor MRG, Patel AR, Wilmot I, Thrush P, Vargas JD, Soslow JH, Becker JR, Seidman CE, Lakdawala NK, Cirino AL; VANISH Investigators; Burns KM, McMurray JJV, MacRae CA, Solomon SD, Orav EJ, Braunwald E. Valsartan in early-stage hypertrophic cardiomyopathy: a randomized phase 2 trial. Nat Med. 2021 Oct;27(10):1818-1824. doi: 10.1038/s41591-021-01505-4. Epub 2021 Sep 23.

    PubMed 34556856

  • Axelsson Raja A, Shi L, Day SM, Russell M, Zahka K, Lever H, Colan SD, Margossian R, Hall EK, Becker J, Jefferies JL, Patel AR, Choudhury L, Murphy AM, Canter C, Bach R, Taylor M, Mestroni L, Wheeler MT, Benson L, Owens AT, Rossano J, Lin KY, Pahl E, Pereira AC, Bundgaard H, Lewis GD, Vargas JD, Cirino AL, McMurray JJV, MacRae CA, Solomon SD, Orav EJ, Braunwald E, Ho CY. Baseline Characteristics of the VANISH Cohort. Circ Heart Fail. 2019 Dec;12(12):e006231. doi: 10.1161/CIRCHEARTFAILURE.119.006231. Epub 2019 Dec 9.

    PubMed 31813281

  • Lee TM, Hsu DT, Kantor P, Towbin JA, Ware SM, Colan SD, Chung WK, Jefferies JL, Rossano JW, Castleberry CD, Addonizio LJ, Lal AK, Lamour JM, Miller EM, Thrush PT, Czachor JD, Razoky H, Hill A, Lipshultz SE. Pediatric Cardiomyopathies. Circ Res. 2017 Sep 15;121(7):855-873. doi: 10.1161/CIRCRESAHA.116.309386.

    PubMed 28912187

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Valsartan in people with Hypertrophic Cardiomyopathy, run by Carelon Research at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite z-score (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01912534, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2021.

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