Developing a diagnostic kit for aortic valve stenosis

Development of a Serum and Cellular Biomarkers Cluster for the Assessment of Degenerative Aortic Valve Stenosis Progression.

This study is testing a new blood test to help doctors diagnose and understand how serious aortic valve stenosis is, so they can better treat patients who might be at risk.

Quick facts

• Study type: Observational
• Enrollment: 280 (estimated)
• Ages: 60 Years to 87 Years
• Sex: All
• Sponsor: National and Kapodistrian University of Athens (other)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Athens, Attiki and 1 other locations)
• Trial ID: NCT04312139 on ClinicalTrials.gov

What this trial studies

AthenaValve aims to create and validate a novel serum diagnostic kit to assess the severity and prognosis of aortic valve stenosis, a serious condition that often goes undiagnosed in its early stages. The study will utilize serum samples from two clinical cohorts and an animal model to develop a multiplexed Enzyme-linked Immunosorbent Assay kit. Advanced bioinformatics will be employed to identify promising biomarkers from integrated data sources. This approach seeks to enable early diagnosis and pave the way for new pharmaceutical therapies for patients at high risk.

Who should consider this trial

Good fit: Ideal candidates include patients with severe or moderate aortic valve stenosis as determined by echocardiography.

Not a fit: Patients with mild aortic valve stenosis or those without aortic valve disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to earlier diagnosis and improved treatment options for patients with aortic valve stenosis.

How similar studies have performed: Previous studies have suggested that early intervention in aortic valve stenosis may improve outcomes, indicating potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

* Retrospective cohort: patients with severe aortic valve stenosis in echocardiography:

  • Vmax \> 4 m/sec and mean Gradient \>40 mmHg and/or Aortic Valve Area indexed (AVAi) \< 0.6 cm2/m2 and/or Velocity index \<0.25 whichever worse, with available complete past echocardiographic follow-up (\>2 past studies) indicating disease progression, by the same performing physician.
* Prospective cohort: patients with moderate aortic valve stenosis in echocardiography:

  * Vmax 3-4 m/sec and mean Gradient 25-40 mmHg and/or AVAi 0.6-0.9 cm2/m2,
  * Where inconsistent: Velocity index = 0.25-0.50.
  * Technical details: Optimal doppler measurements obtained by the best feasible echocardiographic window (demonstrating at least 2 windows, where possible including right parasternal with or without pencil probe).
* Prospective Control group: patients at intermediate to high risk for CVD according to atherosclerotic risk factors assessment - Heart Score

Exclusion Criteria:

* Echocardiographic Stroke Volume indexed (SVi) \<35 ml/m2
* Bicuspid aortic valve
* Stenosis of rheumatic etiology
* More than mild aortic valve regurgitation
* More than mild mitral valve regurgitation
* More than mild mitral stenosis
* Severe pulmonary hypertension
* Chronic ischemic heart failure with Ejection Fraction \< 45%
* Right heart failure (based on the echocardiographic assessment of Right Ventricle Dimension, Tricuspid Annular Plane Systolic Excursion, tricuspid annular velocity, and clinical syndrome)
* Acutely decompensated Heart Failure with preserved Ejection Fraction \<4 weeks
* N-terminal-pro hormone Brain Natriuretic Peptide (NT-proBNP)\> 900 pg/ml for ages 60-75, NT-pro-BNP \> 1800 pg/ml for ages \>75 years
* Presence of chronic systematic inflammatory disease
* Presence of autoimmune disease
* Active malignancy
* History of chemotherapy past 3 years
* Any history of thoracic radiotherapy
* Active treatment with monoclonal antibodies
* Under-treated hypertension
* Under-treated metabolic or endocrine disease
* Acute infection (\<4 weeks)
* Any acute inflammation (\<4 weeks)
* Unstable angina - myocardial infarction past 3 moths
* Stage 4 or 5 Chronic Kidney Disease (as defined by CKD-EPI derived estimated Glomerular Filtration Rate or 24hr urine measurement)
* Any acute renal failure \<4 weeks
* Stroke past 3 months
* Any disabling stroke
* Surgery except for minor procedures past 3 months
* Poor mobility/immobilization
* Life expectancy \< 3 years for any reason
* Difficulty in following follow-up protocol for any reason

For the control group:

* Known coronary artery disease
* Any heart valve disease, excluding minor valve regurgitation
* Any heart failure
* Pulmonary Hypertension
* Peripheral artery disease
* Presence of chronic systematic inflammatory disease
* Presence of autoimmune disease
* Active malignancy
* History of chemotherapy past 3 years
* Any history of thoracic radiotherapy
* Active treatment with monoclonal antibodies
* Under-treated hypertension
* Under-treated metabolic or endocrine disease
* Acute infection (\<4 weeks)
* Any acute inflammation (\<4 weeks)
* Stage 4 or 5 Chronic Kidney Disease, as defined by the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) derived estimated Glomerular Filtration Rate or 24hr urine measurement
* Any acute renal failure \<4 weeks
* Any stroke
* Surgery except for minor procedures past 3 months
* Poor mobility/immobilization
* Life expectancy \< 3 years for any reason
* Difficulty in following follow-up protocol for any reason

Where this trial is running

Athens, Attiki and 1 other locations

• First Department of Cardiology, University of Athens, Medical School. Hippocratio Hospital — Athens, Attiki, Greece (RECRUITING)
• Naval Hospital of Athens — Athens, Greece (RECRUITING)

Study contacts

• Principal investigator: Konstantinos P Toutouzas, Professor — First Department of Cardiology, Athens Medical School, NKUA
• Study coordinator: Nikolaos Anousakis-Vlachochristou, MD

Conditions: Calcific Aortic Valve Disease, Aortic Valve Stenosis, Aortic Valve, Calcification of, aortic valve stenosis, calcific aortic valve disease, aortic stenosis, biomineralization, calcification