Mavacamten Enables Exercise in Hypertrophic Obstructive Cardiomyopathy

NCT07077005 | Recruiting

• 1 other identifier: 2025-125-S-SB
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with hypertrophic obstructive cardiomyopathy and New York Heart Association Class I-II under stable treatment with mavacamten (at least 12 weeks without change of dosage) and a peak left ventricular outflow tract obstruction \<50mmHg undergo either 6 weeks of structured moderate intensity endurance and resistance training (supervised, 3x/week, intervention, IT) or usual care (UC). Patients within 1 hour of travel to the training venue will be referred to IT, while those with more than 1 hour will join UC. At baseline (visit 1, V1) and after 6 weeks of exercise intervention (visit 2, V2) all patients undergo a medical exam, resting and stress echocardiography and receive a questionnaire on the quality of life (Kansas City Cardiomyopathy Questionnaire). Cardiac biomarkers are assessed. 3 hours after stress echocardiography cardiopulmonary exercise testing is performed to measure peak oxygen consumption (VO2peak). The primary outcome is safety. Secondary outcomes include the change of VO2peak, changes in cardiac biomarkers, resting and stress echocardiographic variables, quality of life and variables of cardiopulmonary exercise testing from V1 to V2.

Conditions

Cardiomyopathy, Hypertrophic

Keywords

exercise capacity; mavacamten; safety; exercise training

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Safety is defined by the abscence of adverse or serious adverse events during exercise training or within 1h of exercise termination. Adverse events include non-sustained ventricular tachycardia (nsVT) and atrial fibrillation. Serious adverse events contain hospitalization due to cardiovascular events, sustained ventricular tachycardia, nsVT with hemodynamic compromise, syncope, cardiac arrest and sudden cardiac death. Higher scores mean a worse outcome.

  6 weeks

Secondary Outcomes (7)

• Change of resting left ventricular ejection fraction

  6 weeks

• Change of tissue Doppler velocity during peak exercise

  6 weeks

• Change of minute ventilation to carbon dioxide production

  6 weeks

• Change of Kansas City Cardiomyopathy Score

  6 weeks

• Change of N-terminal pro-B-type natriuretic peptide and troponin I

  6 weeks

Study Arms (2)

Exercise

EXPERIMENTAL

Supervised combined endurance and resistance training on top of mavacamten therapy

Other: Exercise training

Usual Care

NO INTERVENTION

No supervised exercise training

Interventions

Exercise training OTHER

Supervised, combined endurance and resistance training

Exercise

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years of age
• Diagnosis of hypertrophic obstructive cardiomyopathy
• ≥12 weeks of unchanged dosage of mavacamten
• Peak left ventricular outflow tract gradient ≤ 50 mmHg at rest and during stress echocardiography
• New York Heart Association classes I-II

You may not qualify if:

• Corrected QT-interval (Fridericia-formula) ≥ 500 ms
• Paroxysmal or intermittent atrial fibrillation (AF) on screening electrocardiogram
• Persistent or permanent AF without anticoagulation for ≥4 weeks
• Previous transcoronary ablation of septal hypertrophy or surgical myectomy
• Ventricular tachycardia, significant ST-elevation or depression upon baseline cardiopulmonary exercise testing
• ≥ grade II valve insufficiencies or stenoses during resting echocardiography
• Prior implantable cardioverter defibrillator-implantation
• Sudden Cardiac Death Risk Score ≥4%

Sponsors & Collaborators

• Technical University of Munich: lead

Study Sites (1)

Technical University Munich

Munich, Bavaria, 81675, Germany

RECRUITING

Related Publications (12)

• Sachdev V, Sharma K, Keteyian SJ, Alcain CF, Desvigne-Nickens P, Fleg JL, Florea VG, Franklin BA, Guglin M, Halle M, Leifer ES, Panjrath G, Tinsley EA, Wong RP, Kitzman DW; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and American College of Cardiology. Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation. 2023 Apr 18;147(16):e699-e715. doi: 10.1161/CIR.0000000000001122. Epub 2023 Mar 21.

  PMID: 36943925 RESULT

• Ommen SR, Ho CY, Asif IM, Balaji S, Burke MA, Day SM, Dearani JA, Epps KC, Evanovich L, Ferrari VA, Joglar JA, Khan SS, Kim JJ, Kittleson MM, Krittanawong C, Martinez MW, Mital S, Naidu SS, Saberi S, Semsarian C, Times S, Waldman CB; Peer Review Committee Members. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2024 Jun 4;149(23):e1239-e1311. doi: 10.1161/CIR.0000000000001250. Epub 2024 May 8.

  PMID: 38718139 RESULT

• Bertero E, Canepa M, Olivotto I. Hypertrophic cardiomyopathy evolving management: American Heart Association/American College of Cardiology vs. European Society of Cardiology guidelines. Eur Heart J. 2025 Jan 21;46(4):359-361. doi: 10.1093/eurheartj/ehae507. No abstract available.

  PMID: 39504436 RESULT

• Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, Basso C, Bezzina CR, Biagini E, Blom NA, de Boer RA, De Winter T, Elliott PM, Flather M, Garcia-Pavia P, Haugaa KH, Ingles J, Jurcut RO, Klaassen S, Limongelli G, Loeys B, Mogensen J, Olivotto I, Pantazis A, Sharma S, Van Tintelen JP, Ware JS, Kaski JP; ESC Scientific Document Group. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023 Oct 1;44(37):3503-3626. doi: 10.1093/eurheartj/ehad194. No abstract available.

  PMID: 37622657 RESULT

• Kim JH, Baggish AL, Levine BD, Ackerman MJ, Day SM, Dineen EH, Guseh Ii JS, La Gerche A, Lampert R, Martinez MW, Papadakis M, Phelan DM, Shafer KM; American Heart Association Leadership Committee of the Council on Clinical Cardiology; Council on Basic Cardiovascular Sciences; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Peripheral Vascular Disease; American College of Cardiology; Allen LA, Borjesson M, Braverman AC, Brothers JA, Castelletti S, Chung EH, Churchill TW, Claessen G, D'Ascenzi F, Darden D, Dean PN, Dickert NW, Drezner JA, Economy KE, Eijsvogels TMH, Emery MS, Etheridge SP, Gati S, Gray B, Halle M, Harmon KG, Hsu JJ, Kovacs RJ, Krishnan S, Link MS, Maron M, Molossi S, Pelliccia A, Salerno JC, Shah AB, Sharma S, Singh TK, Stewart KM, Thompson PD, Wasfy MM, Wilhelm M. Clinical Considerations for Competitive Sports Participation for Athletes With Cardiovascular Abnormalities: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol. 2025 Mar 18;85(10):1059-1108. doi: 10.1016/j.jacc.2024.12.025. Epub 2025 Feb 20.

  PMID: 39976316 RESULT

• Basu J, Nikoletou D, Miles C, MacLachlan H, Parry-Williams G, Tilby-Jones F, Bulleros P, Fanton Z, Baker C, Purcell S, Lech C, Chapman T, Sage P, Wahid S, Sheikh N, Jayakumar S, Malhotra A, Keteepe-Arachi T, Gray B, Finocchiaro G, Carr-White G, Behr E, Tome M, O'Driscoll J, Chis Ster I, Sharma S, Papadakis M. High intensity exercise programme in patients with hypertrophic cardiomyopathy: a randomized trial. Eur Heart J. 2025 May 14;46(19):1803-1815. doi: 10.1093/eurheartj/ehae919.

  PMID: 40037382 RESULT

• Olivotto I, D'Ascenzi F. Exercise prescription in hypertrophic cardiomyopathy: Dr Lown's lesson to break taboos. Eur Heart J. 2025 May 14;46(19):1816-1818. doi: 10.1093/eurheartj/ehae659. No abstract available.

  PMID: 40037289 RESULT

• Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, Saberi S, Lakdawala NK, Wheeler MT, Owens A, Kubanek M, Wojakowski W, Jensen MK, Gimeno-Blanes J, Afshar K, Myers J, Hegde SM, Solomon SD, Sehnert AJ, Zhang D, Li W, Bhattacharya M, Edelberg JM, Waldman CB, Lester SJ, Wang A, Ho CY, Jacoby D; EXPLORER-HCM study investigators. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Sep 12;396(10253):759-769. doi: 10.1016/S0140-6736(20)31792-X. Epub 2020 Aug 29.

  PMID: 32871100 RESULT

• Wheeler MT, Olivotto I, Elliott PM, Saberi S, Owens AT, Maurer MS, Masri A, Sehnert AJ, Edelberg JM, Chen YM, Florea V, Malhotra R, Wang A, Oreziak A, Myers J. Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial. JAMA Cardiol. 2023 Mar 1;8(3):240-247. doi: 10.1001/jamacardio.2022.5099.

  PMID: 36652223 RESULT

• Lampert R, Ackerman MJ, Marino BS, Burg M, Ainsworth B, Salberg L, Tome Esteban MT, Ho CY, Abraham R, Balaji S, Barth C, Berul CI, Bos M, Cannom D, Choudhury L, Concannon M, Cooper R, Czosek RJ, Dubin AM, Dziura J, Eidem B, Emery MS, Estes NAM, Etheridge SP, Geske JB, Gray B, Hall K, Harmon KG, James CA, Lal AK, Law IH, Li F, Link MS, McKenna WJ, Molossi S, Olshansky B, Ommen SR, Saarel EV, Saberi S, Simone L, Tomaselli G, Ware JS, Zipes DP, Day SM; LIVE Consortium. Vigorous Exercise in Patients With Hypertrophic Cardiomyopathy. JAMA Cardiol. 2023 Jun 1;8(6):595-605. doi: 10.1001/jamacardio.2023.1042.

  PMID: 37195701 RESULT

• Maron BJ, Rowin EJ, Bonaventura J, Basso C, Corrado D, Thiene G, Churchwell AL, Basilico F, Thompson PD, Nishimura RA, Estes NAM. Commentary: Sudden death in competitive student-athletes with hypertrophic cardiomyopathy at a crossroads: Critical views on liberalizing return-to-play eligibility. Heart Rhythm. 2026 Mar;23(3):688-695. doi: 10.1016/j.hrthm.2025.06.014. Epub 2025 Jun 19. No abstract available.

  PMID: 40543859 RESULT

• Pelliccia A, Sharma S, Gati S, Back M, Borjesson M, Caselli S, Collet JP, Corrado D, Drezner JA, Halle M, Hansen D, Heidbuchel H, Myers J, Niebauer J, Papadakis M, Piepoli MF, Prescott E, Roos-Hesselink JW, Graham Stuart A, Taylor RS, Thompson PD, Tiberi M, Vanhees L, Wilhelm M; ESC Scientific Document Group. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J. 2021 Jan 1;42(1):17-96. doi: 10.1093/eurheartj/ehaa605. No abstract available.

  PMID: 32860412 RESULT

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

Exercise

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Simon Wernhart, MD

CONTACT

00498941406774; simon.wernhart@mri.tum.de

Martin Halle, Professor

CONTACT

00498941406774; martin.halle@mri.tum.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The investigator will have no knowledge of group allocation.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients will be allocated to an exercise intervention group undergoing combined endurance and resistance training for 6 weeks or to a usual care group.

Study Record Dates

• First Submitted: July 10, 2025
• First Posted: July 22, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)