Obstructive Hypertrophic Cardiomyopathy
Conditions
Keywords
Obstructive hypertrophic cardiomyopathy, Obstructive HCM (oHCM), Mavacamten, Heart failure, oHCM
Brief summary
This registry evaluates patient characteristics, real-world treatment patterns, and short- and long-term outcomes in a population of patients in the United States and Europe with symptomatic obstructive hypertrophic cardiomyopathy (HCM) who are receiving mavacamten, receiving other treatment for obstructive HCM, or not receiving treatment for obstructive HCM due to intolerance or failure of prior treatment. United States Sub-Study: The purpose of this study is to evaluate the safety of mavacamten in patients with symptomatic obstructive HCM in the real-world setting. Europe Sub-Study: The purpose of this study is to evaluate the effectiveness and safety of mavacamten in patients with symptomatic obstructive HCM in the real-world setting.
Interventions
DRUGMavacamten
As per product label
DRUGNon-mavacamten symptomatic oHCM therapy
Including Beta-blocker (BB), non-dihydropyridine (non-DHP) calcium channel blocker (CCB) and/or disopyramide as per product label
Sponsors
Bristol-Myers Squibb
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age at the time of informed consent. * Willing and able to provide written informed consent form (ICF) and any required privacy authorization prior to the initiation of study procedures (or in those situations where consent cannot be given by participants, consent provided by their legally acceptable representatives) United States Sub-Study * Diagnosis of obstructive HCM consistent with 2020 American Heart Association/American College of Cardiology (AHA/ACC) guidelines. * Obstructive HCM is defined clinically by the presence of increased LV wall thickness ≥ 15 mm (or ≥ 13 mm with positive family history of HCM) in a nondilated ventricular chamber that is not solely explained by abnormal loading conditions (eg, another cardiac or systemic disease) and peak LVOT gradient of ≥ 30 mmHg at rest or with provocation. * Has documented LVEF of ≥ 55% recorded by echocardiography within the last 6 months. * Symptoms consistent with NYHA functional class II-IV. * Receiving beta blocker (BB)s, non-dihydropyridine calcium. channel blockers (nonDHP CCBs), disopyramide, and/or mavacamten (once available) as part of routine clinical care; or currently receiving no treatment due to intolerance or failure of prior treatment (eg, BBs, non-DHP CCBs, or disopyramide) for obstructive HCM. European Sub-study * Diagnosis of obstructive HCM consistent with the most recent European Society of Cardiology (ESC) and American Heart Association/American College of Cardiology (AHA/ACC) guidelines * Documented LVEF of ≥55% recorded by TTE * Documented symptoms consistent with NYHA functional class II-III at enrollment or within 6 months prior to enrollment (if not available at enrollment). * As part of routine clinical care for obstructive HCM: receiving BBs, non-DHP CCBs, disopyramide; initiating mavacamten at enrollment; or currently receiving no treatment due to intolerance or failure of prior treatment (e.g., BBs, non-DHP CCBs, or disopyramide).
Exclusion criteria
* Known phenocopy disease (e.g., Fabry disease, amyloidosis) or LV hypertrophy associated with hypertension. * Documentation of any fixed obstruction of the outflow tract such as aortic valve stenosis or replacement. * Prior treatment of obstructive HCM with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation \[ASA\]) within 6 months prior to enrollment; participants with an unsuccessful myectomy or percutaneous ASA performed \> 6 months prior to enrollment may be enrolled. * Naïve to treatment for obstructive HCM (ie, never treated with BBs, nonDHP CCBs, or disopyramide). United States Sub-Study * Receiving an investigational therapeutic agent for obstructive HCM (eg, myosin-inhibitors other than mavacamten) in an interventional clinical trial at participant enrollment. * Previously or currently enrolled in a long-term safety extension study of mavacamten (eg, EXPLORER-HCM \[ClinicalTrials.gov, NCT03470545\], MAVA-LTE \[NCT03723655\], PIONEER-OLE \[NCT03496168\], VALORHCM \[NCT04349072\], or MAVERICK \[NCT03442764\]) European Sub-study * Receiving an investigational therapeutic agent or any cardiac myosin inhibitor and/or modulators for obstructive HCM at patient enrolment * Previously or currently enrolled in other HCM registry studies (e.g., TORCH, REMY, EU-PASS) * Previously or currently enrolled in a study of mavacamten (e.g., EXPLORER-HCM \[ClinicalTrials.gov, NCT03470545\], MAVA-LTE \[NCT03723655\], PIONEER-OLE \[NCT03496168\], VALOR-HCM \[NCT04349072\], MAVERICK \[NCT03442764\], or MEMENTO \[NCT2264899\]) * Previously treated with mavacamten
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence rate of new or worsening heart failure due to systolic dysfunction among participants with symptomatic obstructive HCM during periods of exposure to mavacamten and other oHCM treatment | Up to 5 Years | Systolic dysfunction defined as symptomatic Left Ventricular Ejection Fraction (LVEF) \< 50%. United States participants only. |
| Change in resting left ventricular outflow tract (LVOT) gradient from baseline | Up to 18 months | European Participants only |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of arrhythmia | Baseline, and up to 18 months (European participants), or 5 Years (United States participants) | Incidence rates of participants with arrhythmia (new onset) |
| New or worsening heart failure due to systolic dysfunction | Baseline and up to 18 months | Symptomatic left ventricular ejection fraction (LVEF) \<50%. European Participants only |
| Proportion of participants with a resting or provoked peak left ventricular outflow tract (LVOT) gradient below 50 mmHG | Baseline and up to 18 months | European participants only |
| Proportion of participants with a resting or provoked peak left ventricular outflow tract (LVOT) gradient below 30 mmHG | Baseline and up to 18 months | European participants only |
| Occurrence of Major Adverse Cardiovascular Events (MACE) | Up to 5 Years | A composite endpoint consisting of non-fatal acute Myocardial Infarction (MI), stroke, hospitalization due to Heart Failure (HF) and Cardiovascular (CV) mortality. United States participants only. |
| Occurrence of non-fatal acute Myocardial Infarction (MI) | Up to 5 Years | United States participants only |
| Occurrence of Stroke | Up to 5 Years | United States participants only |
| Occurrence of hospitalization due to heart failure | Baseline, and up to 18 months (European participants), or 5 Years (United States participants) | — |
| Occurrence of cardiovascular mortality | Up to 5 Years | United States participants only |
| Occurrence of all-cause mortality | Baseline, and up to 18 months (European participants), or 5 Years (United States participants) | — |
| Evaluation of functional responses: New York Heart Association (NYHA) function class | Baseline, and up to 18 months (European participants), or 5 Years (United States participants) | Percentage of Participants Whose NYHA Class Changes |
| Evaluation of functional responses: Left Ventricular Outflow Tract (LVOT) gradient | Baseline, and up to 18 months (European participants), or 5 Years (United States participants) | Mean Change From Baseline in LVOT Gradients At Rest and Provoked |
| Evaluation of functional responses: LVEF | Baseline, and up to 18 months (European participants), or 5 Years (United States participants) | Mean Change from Baseline in LVEF |
| Evaluation of patient reported outcome measure: Kansas City Cardiomyopathy Questionnaire 23 (KCCQ-23) | Baseline, and up to 5 Years | The KCCQ-23 is a disease-specific health status instrument composed of 23 items that quantifies the domains of physical limitations, symptoms, self-efficacy, social limitation and quality of life from heart failure. Scores range from 0-100, in which higher scores reflect better health status. United States participants only |
| Evaluation of patient reported outcome measure: EuroQol Five Dimensions Questionnaire (5-level) (EQ-5D-5L): Health Utility Index | Baseline, and up to 5 Years | The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L health utility index and EQ Visual Analog Scale (VAS). EQ-5D-5L health utility index is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participants select an answer for each of the 5 dimensions that best matches his/her health "today". Responses are used to generate a weighted summary index, which ranges from 0 to 1.00. A higher score indicates better health and positive changes from baseline indicate improvement of health. United States participants only |
| Evaluation of patient reported outcome measure: EQ-5D-5L: VAS | Baseline, and up to 5 Years | The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and VAS. The VAS self-rating records the participant's own assessment of his or her overall health status at the time of completion, on a vertical line VAS with scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine). A higher score indicates better health and positive changes from baseline indicate improvement of health status. United States participants only |
| Evaluation of biomarkers of response: NT-proBNP | Baseline, and up to 5 Years | Change From Baseline in Serum concentration of NT-proBNP. United States participants only |
| Evaluation of biomarkers of response: Cardiac troponin | Baseline, and up to 5 Years | Change From Baseline in Serum Concentration of Cardiac Troponins. United States participants only |
Countries
Austria, Czechia, France, Germany, Poland, Puerto Rico, Spain, United Kingdom, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed