Obstructive Hypertrophic Cardiomyopathy (oHCM)
Conditions
Brief summary
This study aims to evaluate whether, under a treatment strategy primarily guided by left ventricular ejection fraction (LVEF), dose up-titration in adult patients with symptomatic obstructive hypertrophic cardiomyopathy who have received Mavacamten treatment for at least 12 weeks with a stable maintenance dose (as baseline) and with LVEF ≥55% can further reduce left ventricular outflow tract (LVOT) gradient after 24 weeks of treatment. It will also assess changes in hemodynamics, clinical symptoms, cardiac structure, and function. Furthermore, the study will conduct stratified analyses based on patients' baseline resting or Valsalva-provoked LVOT gradient levels at enrollment \[\<30 mmHg vs. ≥30 mmHg\] to explore differences in the aforementioned outcome measures among patients with different gradient levels, with the goal of providing evidence for individualized clinical dose adjustment.
Interventions
DRUGMavacamten
Eligible participants will undergo dose escalation at baseline from their current dose to the next higher level (once daily: 2.5 mg → 5 mg, 5 mg → 10 mg, or 10 mg → 15 mg). At Week 4, clinical status and echocardiography will be re-evaluated, and the same dose will be maintained for the subsequent 8 weeks, unless LVEF is \< 50%. After 12 weeks of treatment at the same dose level: If LVEF remains ≥ 55%, further dose escalation is permitted. If LVEF is between 50% and 55%, the current dose will be maintained. If LVEF is \< 50%, treatment will be interrupted/discontinued.
Sponsors
Second Affiliated Hospital of Nanchang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Adult patients diagnosed with obstructive hypertrophic cardiomyopathy (HCM) and classified as New York Heart Association (NYHA) functional class II-III. 2. Have received stable Mavacamten treatment for at least 12 weeks with a stable dose. 3. LVEF ≥ 55%.
Exclusion criteria
* 1\. Hypertrophy caused by other systemic diseases with a clear etiology. 2. Planned use of strong CYP2C19 inhibitors, moderate to strong CYP2C19 inducers, or CYP3A4 inducers during the study. 3. Planned use of disopyramide, ranolazine, verapamil combined with beta-blockers, or diltiazem combined with beta-blockers during the study. 4. Previous intolerance to Mavacamten. 5. Severe hepatic or renal dysfunction. 6. Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Valsalva Peak Left Ventricular Outflow Tract (LVOT) Pressure Gradient Assessed by Echocardiography at Week 24 | Baseline, Week 4, Week 8, Week 12, and Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Wall Thickness | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
| Left Atrial Volume Index | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
| Left Ventricular Mass Index | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
| Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) | Baseline and Week 24 | The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) includes the physical limitation and total symptom domains. Scores range from 0 to 100, where higher scores indicate better health status, fewer symptoms, and less physical limitation (a better outcome). |
| Mitral Regurgitation Severity | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
| Systolic Anterior Motion | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
| E/A Ratio | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
| Left Ventricular Ejection Fraction | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
| New York Heart Association (NYHA) Functional Class | Baseline, Week 4, Week 8, Week 12, and Week 24 | Assessed by the New York Heart Association (NYHA) Functional Classification. The classification categorizes heart failure severity into four classes: Class I (no limitation of physical activity), Class II (slight limitation), Class III (marked limitation), and Class IV (unable to carry on any physical activity without discomfort). Scores range from Class I to Class IV, where higher classes indicate worse heart failure symptoms (a worse outcome) |
| NT-proBNP | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
| Myocardial troponin | Baseline, Week 4, Week 8, Week 12, and Week 24 | — |
Contacts
CONTACTPing Li
Outcome results
None listed