Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)

RASopathy-associated hypertrophic cardiomyopathy (RAS-CM) is a disease with high morbidity and high mortality if presenting during infancy. Targeted therapies have shown significant activity in preclinical models and case reports. Drugs that target the underlying cause of this disease are now developed in cancer patients. Conducting randomized trials is not possible in severely ill infants with RAS-CM. Existing historical controls from older eras are not sufficient as external controls to support drug development as they lack critical clinical and genetic information to allow comparison with the cohort planned for future clinical trials.

The purpose of this investigator-initiated retrospective natural history study is to collect clinical information and genetic information in patients with RAS-CM. The first goal is to establish a data set that meets regulatory requirements for the use as external control data in a future clinical trial, composing non-randomized, single-arm, open-label study cohorts. The second goal is to obtain natural history information that supports the selection of secondary exploratory endpoints chosen in a clinical trial.

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Key information

Conditions

Hypertrophic Cardiomyopathy (HCM) Aortic Stenosis, Subvalvular Aortic Valve Disease Aortic Valve Stenosis Cardiomyopathies Cardiomyopathy, Hypertrophic Cardiovascular Diseases Heart Diseases Heart Failure Heart Valve Diseases RASopathy

Sex eligibility

All sexes

Study type

Observational

Primary location

TUM Klinikum Deutsches Herzzentrum München

München, 80636, Germany

Location status: Recruiting

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Molecular genetic diagnosis of a RASopathy (i.e., a pathogenic or likely pathogenic variant in one of the RAS-MAPK pathway genes identified, irrespective of when performed)
Imaging diagnosis of myocardial hypertrophy (echocardiography) showing a maximal end-diastolic wall thickness of greater than normal (z-score > 2) with or without outflow tract obstruction
Admitted to hospital between 01/01/2015 and 06/30/2019 for congestive heart failure* or developing progressive congestive heart failure during any hospital stay within first 6 months of life**

Ross score calculated from medical history and physical examination notes in the absence of any other reason prompting hospital admission (e.g., elective procedure, other organ dysfunction, etc.); **: defined by Ross Score greater than 2

Exclusion criteria

Receiving mechanistic Target of Rapamycin Inhibitor (mTOR inhibitor) and/or Mitogen-Activated Protein Kinase Kinase Inhibitor (MEK inhibitors)
Inability to identify or retrospectively calculate the patient´s Ross Score within the first six months of life

Treatment and study plan

Retrospective data collection

Other

Retrospective data collection, observation group are patients with genetic diagnosis of congenital RASopathy with hypertrophic cardiomyopathy and heart failure

Primary outcomes

To define the one-year transplant-free survival rate of patients with infantile-onset RASopathy-associated hypertrophic cardiomyopathy, admitted to the hospital with congestive heart failure by 6 months of age.

Time frame: Admitted to hospital between 01/01/2015 and 06/30/2019 for congestive heart failure* or developing progressive congestive heart failure during any hospital stay within first 6 months of life**

Study contacts

Contact information is provided by the study sponsor or research team.

Cordula Prof. Wolf

CONTACT

[email protected]

+49 89 1218-2441

Sponsors and collaborators

Lead sponsor

Deutsches Herzzentrum Muenchen

Other

Registry information

Acronym: RAS-CM

Important dates

Study start: 2025
Primary completion: 2026
Study completion: 2026
First posted: Jan 15, 2026
Registry last updated: Feb 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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