Clinical trial NCT05489705: A Prospective Registry Study to Assess Real-world Patient Characteristics, Treatment Patterns, and Longitudinal Outcomes in Patients Receiving Mavacamten and Other Treatments for Symptomatic Obstructive Hypertrophic Cardiomyopathy (Obstructive-HCM)
Official title: Deliver Insights in Hypertrophic Cardiomyopathy and Observational Outcomes in Real World: United States and European Prospective Registry Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obstructive Hypertrophic Cardiomyopathy
Keywords: Obstructive hypertrophic cardiomyopathy
Obstructive HCM (oHCM)
Mavacamten
Heart failure
oHCM
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2022-08-05
Enrollment: 1600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will include adult participants with symptomatic obstructive HCM who are receiving pharmacological treatment for obstructive HCM (for example, BBs, non-DHP CCBs, disopyramide, and/or mavacamten) as part of routine care in the United States or Europe.

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Up to 5 Years
measure: Change in resting left ventricular outflow tract (LVOT) gradient from baseline
timeFrame: Up to 18 months
Secondary outcomes:
measure: Occurrence of arrhythmia
timeFrame: Baseline, and up to 18 months (European participants), or 5 Years (United States participants)
measure: New or worsening heart failure due to systolic dysfunction
timeFrame: Baseline and up to 18 months
measure: Proportion of participants with a resting or provoked peak left ventricular outflow tract (LVOT) gradient below 50 mmHG
timeFrame: Baseline and up to 18 months
measure: Proportion of participants with a resting or provoked peak left ventricular outflow tract (LVOT) gradient below 30 mmHG
timeFrame: Baseline and up to 18 months
measure: Occurrence of Major Adverse Cardiovascular Events (MACE)
timeFrame: Up to 5 Years
measure: Occurrence of non-fatal acute Myocardial Infarction (MI)
timeFrame: Up to 5 Years
measure: Occurrence of Stroke
timeFrame: Up to 5 Years
measure: Occurrence of hospitalization due to heart failure
timeFrame: Baseline, and up to 18 months (European participants), or 5 Years (United States participants)
measure: Occurrence of cardiovascular mortality
timeFrame: Up to 5 Years
measure: Occurrence of all-cause mortality
timeFrame: Baseline, and up to 18 months (European participants), or 5 Years (United States participants)
measure: Evaluation of functional responses: New York Heart Association (NYHA) function class
timeFrame: Baseline, and up to 18 months (European participants), or 5 Years (United States participants)
measure: Evaluation of functional responses: Left Ventricular Outflow Tract (LVOT) gradient
timeFrame: Baseline, and up to 18 months (European participants), or 5 Years (United States participants)
measure: Evaluation of functional responses: LVEF
timeFrame: Baseline, and up to 18 months (European participants), or 5 Years (United States participants)
measure: Evaluation of patient reported outcome measure: Kansas City Cardiomyopathy Questionnaire 23 (KCCQ-23)
timeFrame: Baseline, and up to 5 Years
measure: Evaluation of patient reported outcome measure: EuroQol Five Dimensions Questionnaire (5-level) (EQ-5D-5L): Health Utility Index
timeFrame: Baseline, and up to 5 Years
measure: Evaluation of patient reported outcome measure: EQ-5D-5L: VAS
timeFrame: Baseline, and up to 5 Years
measure: Evaluation of biomarkers of response: NT-proBNP
timeFrame: Baseline, and up to 5 Years
measure: Evaluation of biomarkers of response: Cardiac troponin
timeFrame: Baseline, and up to 5 Years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Heart Institute
state: Alaska
city: Tucson
country: United States
facility: Pima Heart and Vascular
state: Arizona
city: Little Rock
country: United States
facility: UAMS
state: Arkansas
city: La Jolla
country: United States
facility: UC San Diego School of Medicine
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC-Usc
state: California
city: Palo Alto
country: United States
facility: Stanford Health Care Hospital & Clinics
state: California
city: San Francisco
country: United States
facility: University Of California San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: UC Denver, AMC
state: Colorado
city: Hartford
country: United States
facility: Hartford HealthCare
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Uf Health Jacksonville
state: Florida
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago Dept of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana. University
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan Physician Network-Indiana Heart Physicians
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University Of Kansas Medical Center & Medical Pavilion
state: Kansas
city: Baltimore
country: United States
facility: University Of Maryland, Ihv
state: Maryland
city: Baltimore
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Boston
country: United States
facility: Harvard (Massachusetts General Hospital)
state: Massachusetts
city: Boston
country: United States
facility: Harvard Medical School - Brigham and Women's Hospital (BWH)
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health Medical Group
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Tupelo
country: United States
facility: Cardiology Associates Research, Llc
state: Mississippi
city: Kansas City
country: United States
facility: St. Luke's Mid-America Heart Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: CHI Health Reseach Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Cooperstown
country: United States
facility: Bassett Medical Center
state: New York
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Roslyn
country: United States
facility: Saint Francis Hospital
state: New York
city: Valhalla
country: United States
facility: WMCHealth Advanced Physician Services
state: New York
city: Charlotte
country: United States
facility: Focus Clinical Research
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Cincinnati
country: United States
facility: Christ Hospital Health Network
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: AHN Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University Of Pittsburgh
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Health System
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health - Upstate
state: South Carolina
city: Nashville
country: United States
facility: Tristar Centennial Medical Ctr
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Health
state: Tennessee
city: Dallas
country: United States
facility: North Texas Cardiology Center
state: Texas
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital, Methodist Cancer Cencer
state: Texas
city: Houston
country: United States
facility: BI Research Center
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White The Heart Hospital Plano
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Centre - Temple
state: Texas
city: Charlottesville
country: United States
facility: The Rector and Visitors of the Univ of Virginia
state: Virginia
city: Richmond
country: United States
facility: VCU Medical Center
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic; Virginia Tech-Carilion School of Medicine
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Morgantown
country: United States
facility: WVU Hospitals
state: West Virginia
city: Madison
country: United States
facility: University Of Wisconsin - Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Inc (PI Address)
state: Wisconsin
city: Braunau am Inn
country: Austria
facility: Local Institution - 0082
city: Graz
country: Austria
facility: Local Institution - 0087
city: Innsbruck
country: Austria
facility: Local Institution - 0088
city: Klagenfurt am Worthersee
country: Austria
facility: Local Institution - 0084
city: Linz
country: Austria
facility: Local Institution - 0086
city: St. Pölten
country: Austria
facility: Local Institution - 0085
city: Wien
country: Austria
facility: Local Institution - 0083
city: Haguenau
country: France
facility: Centre Hospitalier Haguenau
state: Bas Rhin
city: Saint-Herblain
country: France
facility: Local Institution - 0093
state: Loire Atlantique
city: Lille
country: France
facility: Local Institution - 0090
state: Nord
city: Amiens Cedex 1
country: France
facility: Local Institution - 0091
state: Somme
city: Toulon
country: France
facility: Local Institution - 0094
state: Var
city: Poitiers
country: France
facility: Local Institution - 0089
state: Vienne
city: Aalen
country: Germany
facility: Local Institution - 0098
state: Baden Wuerttemberg
city: Erlangen
country: Germany
facility: Local Institution - 0101
state: Bayern
city: Bernau
country: Germany
facility: Local Institution - 0095
state: Berlin
city: Muenster
country: Germany
facility: Local Institution - 0100
state: Nordrhein Westfalen
city: Dresden
country: Germany
facility: Local Institution - 0099
state: Sachsen
city: Leipzig
country: Germany
facility: Local Institution - 0097
state: Sachsen
city: Berlin
country: Germany
facility: Local Institution - 0096
city: Ponce
country: Puerto Rico
facility: Research & Cardiovascular Corp
city: Oviedo
country: Spain
facility: Local Institution - 0106
state: Asturias
city: Palma De Mallorca
country: Spain
facility: Local Institution - 0109
state: Baleares
city: Majadahonda
country: Spain
facility: Local Institution - 0104
state: Madrid
city: El Palmar
country: Spain
facility: Local Institution - 0105
state: Murcia
city: Burgos
country: Spain
facility: Local Institution - 0107
city: Madrid
country: Spain
facility: Local Institution - 0102
city: Madrid
country: Spain
facility: Local Institution - 0108
city: Malaga
country: Spain
facility: Local Institution - 0103
city: London
country: United Kingdom
facility: Local Institution - 0113
state: Greater London
city: London
country: United Kingdom
facility: Local Institution - 0115
state: Greater London
city: Manchester
country: United Kingdom
facility: Local Institution - 0112
state: Greater Manchester
city: Liverpool
country: United Kingdom
facility: Local Institution - 0111
state: Merseyside
city: Birmingham
country: United Kingdom
facility: Local Institution - 0110
state: West Midlands
city: Leeds
country: United Kingdom
facility: Local Institution - 0114
state: West Yorkshire
city: Cardiff
country: United Kingdom
facility: Local Institution - 0116
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: