Clinical trial NCT00538759: Radiation Following Percutaneous Balloon Aortic Valvuloplasty to Prevent Restenosis
Official title: RADiation Following Percutaneous Balloon Aortic Valvuloplasty to Prevent Restenosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Aortic Valve Stenosis
Keywords: Aortic valve stenosis
Balloon aortic valvuloplasty
Aortic valve restenosis
Lead sponsor: Minneapolis Heart Institute Foundation
Sponsor class: OTHER
Collaborators: name: Twin Cities Heart Foundation
name: Minneapolis Heart Institute
First posted: 2007-10-03
Enrollment: 21
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Aortic Valve Area as a Continuous Variable, Measured by Echocardiography
timeFrame: 6 months
measure: Incidence of Major External Beam Radiation Therapy-related Complications
timeFrame: 6 months
Secondary outcomes:
measure: NYHA Improvement
timeFrame: 6 months
measure: CHF Rehospitalization
timeFrame: 6 months
measure: Aortic Valve Reintervention
timeFrame: 6 months
measure: Aortic Valve Area Late Loss Index
timeFrame: 6 months
measure: Aortic Valve Mean Gradient
timeFrame: 6 months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital
state: Minnesota
city: Cincinnati
country: United States
facility: Lindner Clinical Trial Center
state: Ohio
Study officials:
affiliation: Minneapolis Heart Institute Foundation
name: Wes R Pedersen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pedersen WR, Van Tassel RA, Pierce TA, Pence DM, Monyak DJ, Kim TH, Harris KM, Knickelbine T, Lesser JR, Madison JD, Mooney MR, Goldenberg IF, Longe TF, Poulose AK, Graham KJ, Nelson RR, Pritzker MR, Pagan-Carlo LA, Boisjolie CR, Zenovich AG, Schwartz RS. Radiation following percutaneous balloon aortic valvuloplasty to prevent restenosis (RADAR pilot trial). Catheter Cardiovasc Interv. 2006 Aug;68(2):183-92. doi: 10.1002/ccd.20818.