The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction (BRAVE-HCM)

The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction: A Prospective, Interventional, Real-World Clinical Study.

This study is a prospective interventional cohort study aimed at evaluating the therapeutic efficacy and clinical utility of Mavacamten-a targeted myosin inhibitor specifically developed for obstructive hypertrophic cardiomyopathy (HCM)-in patients with HCM characterized by mid-to-apical left ventricular obstruction.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertrophic Cardiomyopathy (HCM)
• Intervention / Treatment: Drug: mavacamten; Drug: Beta Blocker (BB) - metoprolol, bisoprolol, carvedilol; Drug: diltiazem

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xiaojie Xie, MD, PhD; Phone Number: 571-87784700; Email: xiexj@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Second Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Xiaojie Xie, MD, PhD; Phone Number: 571-87784700; Email: xiexj@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with HCM according to the 2023 Chinese Guidelines for the Diagnosis and Treatment of Adult Hypertrophic Cardiomyopathy, meeting one of the following:

  1. Left ventricular wall thickness ≥15 mm at end-diastole in any segment as assessed by echocardiography or cardiac magnetic resonance imaging (CMR);
  2. Left ventricular wall thickness ≥13 mm in individuals with a confirmed pathogenic gene mutation or in genetically affected family members;

  3. Exclusion of other cardiovascular, systemic, or metabolic disorders that may cause ventricular hypertrophy.

     • Symptomatic non-outflow tract obstructive HCM patients (meeting criterion a and at least one of b or c):
  1. Presence of clinical symptoms such as dyspnea, chest pain, dizziness, palpitations, or syncope, with New York Heart Association (NYHA) functional class II-III;
  2. Maximal pressure gradient (PGmax) >30 mmHg in the mid-ventricle under resting or Valsalva maneuver as assessed by echocardiography;

  3. PGmax >30 mmHg in the apical region under resting or Valsalva maneuver on echocardiography.

     ③Ability to provide written informed consent (ICF) and any required privacy authorization prior to study enrollment.

     Exclusion Criteria:

     -

• Obstructive hypertrophic cardiomyopathy (HCM), defined as a maximal left ventricular outflow tract pressure gradient (LVOT-PGmax) ≥30 mmHg at rest and during the Valsalva maneuver on echocardiography;

  • Maximal right ventricular outflow tract pressure gradient (RVOT-PGmax) ≥16 mmHg at rest; ③ Left ventricular ejection fraction (LVEF) <50% on echocardiography;

    • Uncontrolled primary hypertension;

      • Moderate or severe aortic valve stenosis and/or primary mitral valve disease with severe mitral regurgitation; ⑥ Known infiltrative or storage disorders mimicking the HCM phenotype (e.g., Fabry disease, cardiac amyloidosis); ⑦ Presence of severe infections, hepatic dysfunction, renal impairment, or other serious conditions significantly affecting life expectancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mavacamten; Add-on use of mavacamten on top of guideline-directed standard medical therapy	Drug: mavacamten; Add Mavacamten to guideline-directed standard medical therapy for patients with hypertrophic cardiomyopathy (HCM) and mid-to-apical left ventricular obstruction.; Other Names: beta receptor blockers; Drug: Beta Blocker (BB) - metoprolol, bisoprolol, carvedilol; Administer an appropriate dose of beta-blockers according to the patient's tolerance.; Drug: diltiazem; Administer an appropriate dose of diltiazem according to the patient's tolerance.
Active Comparator: No mavacamten; Guideline-directed standard medical therapy group	Drug: Beta Blocker (BB) - metoprolol, bisoprolol, carvedilol; Administer an appropriate dose of beta-blockers according to the patient's tolerance.; Drug: diltiazem; Administer an appropriate dose of diltiazem according to the patient's tolerance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in pressure gradient during the Valsalva maneuver	The percentage reduction in the pressure gradient at the site of left ventricular obstruction during the Valsalva maneuver at week 36, compared to baseline, as measured by echocardiography.	Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in resting pressure gradient	The percentage reduction in the pressure gradient at the site of left ventricular obstruction at rest measured by echocardiography at week 36 compared to baseline.	Week 36
Absolute change in pressure gradient during the Valsalva maneuver	The absolute decrease in number of the pressure gradient at the site of left ventricular obstruction during the Valsalva maneuver measured by echocardiography at week 36 compared to baseline.	Week 36
The proportion of patients with a pressure gradient <30 mmHg during the Valsalva maneuver	The proportion of patients with a pressure gradient <30 mmHg at the site of obstruction during the Valsalva maneuver at week 36.	Week 36
BNP	Number decrease in BNP levels from baseline to week 36.	Week 36
Troponin T	Number decrease in Troponin T levels from baseline to week 36.	Week 36
New-onset atrial fibrillation	Rate of new-onset atrial fibrillation in each group during the study period	From baseline to week 36
LVEF<50%	The proportion of patients in each group with LVEF <50% accompanied by signs and symptoms of heart failure worsening and/or an increase in BNP of ≥30% compared to the previous measurement during the study period.	From baseline to week 36
LVEF<40%	Rate of LVEF <40% in each group during the study period.	From baseline to week 36
Anterior papillary muscle to the interventricular septum distance	Percentage Increase in the distance from the anterior papillary muscle to the interventricular septum	Week 36
Left atrial global longitudinal strain	Left Atrial Global Longitudinal Strain (LA GLS) is an echocardiographic parameter derived from speckle-tracking imaging that measures the longitudinal deformation of the left atrial myocardium throughout the cardiac cycle.	Week 36
Left ventricular global longitudinal strain	Left Ventricular Global Longitudinal Strain (LVGLS) is a sensitive echocardiographic parameter derived from speckle-tracking imaging that quantifies the myocardial deformation in the longitudinal direction. It reflects the shortening of myocardial fibers along the long axis of the left ventricle during systole.	Week 36

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: July 29, 2025
• First Submitted That Met QC Criteria: July 29, 2025
• First Posted (Actual): August 5, 2025

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Cardiomyopathies; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Adrenergic Agents; Adrenergic Antagonists; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmacologic Actions; Chemical Actions and Uses; Amines; Indoles; Alcohols; Benzazepines; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Heterocyclic Compounds, 3-Ring; Carbazoles; Carvedilol; Metoprolol; Bisoprolol; Diltiazem; Adrenergic beta-Antagonists; MYK-461
• Other Study ID Numbers: 2025-1056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No