Radiation Following Percutaneous Balloon Aortic Valvuloplasty to Prevent Restenosis

Study Overview
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Brief Summary
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The objective of the RADAR trial is to determine the impact of External Beam Radiation Therapy (EBRT) on aortic valve restenosis following successful percutaneous balloon aortic valvuloplasty (BAV) in elderly patients with severe calcific aortic stenosis.

Detailed Description
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The RADAR trial is a prospective, randomized, double-blind, sham-controlled, two-stage, adaptive clinical trial. Following successful Balloon Aortic Valvuloplasty, patients with severe aortic stenosis will be randomized in a 2:1 fashion to External Beam Radiation Therapy (EBRT) plus standard medical therapy or standard medical therapy along with sham EBRT (placebo). During Stage One, approximately 110 patients will be enrolled in order to have 80 patients randomized and 66 patients with valid 6 month data. The sample size for Stage Two will be calculated at the end of Stage One. At the time of study commencement, the expectation is that the total sample size will be approximately 155 patients with valid 6-month data, and thus 195 will be randomized and up to 250 enrolled. Patients will be followed for a period of two (2) years. Echocardiographic and clinical endpoint data will be collected and analyzed.

Official Title
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RADiation Following Percutaneous Balloon Aortic Valvuloplasty to Prevent Restenosis

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Device: External beam radiation therapy
* Other: Sham Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Calcific aortic valve stenosis with an echocardiographically derived AV index of less than 0.45 cm2/m2. Any symptoms of severe AS, including near syncope/syncope, angina, excessive fatigue and/or shortness of breath with NYHA functional class II-IV limitation. Age greater than 75 and risk of aortic valve replacement surgery greater than or equal to 15 percent. This may be assessed by using the STS Risk Predictor (see appendix C), confirmed by consultation with a cardiac surgeon experienced in high risk aortic valve surgery OR by having a cardiac surgeon experienced in high risk aortic valve surgery document comorbid conditions (such as porcelain aorta, malnutrition or other comorbidities not captured by the STS scoring system) that make the risk greater than or equal to 15 percent by the estimation of the surgeon. If age greater than or equal to 90 a cardiac surgeon experienced in high risk aortic valve surgery must document that BAV is a better option for the patient than aortic valve replacement surgery. Probable survival greater than 6 months after successful valvuloplasty. Patient is competent, willing to comply with follow-up, understands risks, benefits and alternatives and has signed the Informed Consent form. Exclusion Criteria: Patient has undergone previous BAV or AVR. Patient is undergoing BAV as a bridge to AVR. 4 plus (severe) Aortic insufficiency by echocardiogram obtained prior to planned BAV procedure. Known congenital AV abnormality (e.g., bicuspid AV). ST Elevation Myocardial Infarction (STEMI) associated with CKMB greater than or equal to 3 times ULN or stroke less than or equal to 6 weeks prior to planned BAV procedure. Bacterial endocarditis less than or equal to 1 year prior to planned BAV procedure. Left ventricular ejection fraction less than 30% by preprocedural echocardiography. Baseline mean AV gradient less than 30 mm Hg by echocardiogram unless associated with a left ventricular ejection fraction of less than 40 per cent and true severe AS confirmed by dobutamine stress echocardiogram, i.e., AVA index less than or equal to 0.45cm2/m2 at peak dobutamine infusion. See Appendix D for suggested protocol. Patients who do not achieve successful BAV performed as a part of RADAR Trial: success being defined as an improvement in 4-24 hour post-valvuloplasty echocardiographically-derived AVA that is greater than 35 per cent over baseline and AVA greater than or equal to 0.7 cm2 and the absence of 4+ plus AI. Percutaneous Coronary Intervention with drug eluting stent placement less than or equal to 6 months prior to planned BAV procedure or bare metal stent placement/balloon angioplasty less than or equal to 8 weeks prior to planned BAV procedure. Cardiogenic shock, as defined by a consistent systolic blood pressure less than 80 mm Hg off vasopressors or less than 90 mm Hg on vasopressors. Patients requiring ventilator support less than or equal to 48 hours prior to planned BAV procedure. Creatinine greater than 2.2 mg/dL less than or equal to 48 hours prior to planned BAV procedure. Platelet count less than or equal to 100,000/mm3 less than or equal to 48 hours prior to planned BAV procedure. Hemoglobin less than or equal to 9.0 gm/dL less than or equal to 48 hours prior to planned BAV procedure. Known allergy/sensitivity to ASA. Known allergy/sensitivity to both clopidogrel and ticlopidine. Gastrointestinal bleed requiring transfusion less than or equal to 2 weeks prior to planned BAV procedure. Prior external beam radiation therapy to the chest that, in the judgment of the radiation oncologist, will compromise patient safety or interfere with the interpretation of the study results. This includes any prior radiation to the thoracic contents, except for radiation treatments for malignant or benign lesions of the skin. Untreated pneumonia or other systemic infection associated with fever greater than 38.5˚c or WBC count greater than 10,000 less than or equal to 72 hours prior to planned BAV procedure. Concomitant medical illness (for example, terminal malignancy) that in the opinion of the investigator is associated with reduced survival of less than 6 months. Major surgery less than or equal to 2 weeks prior to planned BAV procedure. Any illness or condition which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of the study results. Involvement in any study of an investigational drug, device or procedure less than or equal to 30 days prior to planned BAV procedure. Previous enrollment in this study.

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBRT<br>External beam radiation therapy to the aortic valve after successful balloon aortic valvuloplasty. | Device: External beam radiation therapy<br>* Experimental beam radiation therapy to the aortic valve after successful balloon aortic valvuloplasty<br>|
| Sham Comparator: Control<br>Sham external beam radiation therapy to the aortic valve after successful balloon aortic valvuloplasty. | Other: Sham Control<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic Valve Area as a Continuous Variable, Measured by Echocardiography |  | 6 months | 
| Incidence of Major External Beam Radiation Therapy-related Complications |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NYHA Improvement | Improvement from pre-procedural NYHA class. Patients' heart failure were graded according to the severity of their symptoms. The New York Heart Association (NYHA) Functional Classification was used. It places patients in one of four categories based on how much they are limited during physical activity. I No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). II Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). III Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. IV Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. | 6 months | 
| CHF Rehospitalization |  | 6 months | 
| Aortic Valve Reintervention |  | 6 months | 
| Aortic Valve Area Late Loss Index | The difference between the Aortic Valve Area at 6 months and the Aortic Valve Area post procedure indexed to the subject | 6 months | 
| Aortic Valve Mean Gradient |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic valve stenosis, Balloon aortic valvuloplasty, Aortic valve restenosis