Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Retrospective data collection.
- Who it may be relevant to
- Registry conditions: Hypertrophic Cardiomyopathy (HCM), Heart Failure, RASopathy. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Germany
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- Other Retrospective data collection
Retrospective data collection, observation group are patients with genetic diagnosis of congenital RASopathy with hypertrophic cardiomyopathy and heart failure
Primary outcome measures
- 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**]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Other
Study locations
Germany · 1 center
- TUM Klinikum Deutsches Herzzentrum München — München
Identifiers
NCT: NCT07344480 · RAS-CM