Angiogenesis in Women With Angina Pectoris Who Are Not Candidates for Revascularization (AWARE)

This is an interventional treatment trial for Angina Pectoris focused on measuring angina, FGF-4, angiogenesis, growth factor, myocardia ischemia, revascularization Read More

Inclusion Criteria:

• Female patients 18-75 years of age inclusive
• Stable angina classified as CCS III or IV
• Receiving treatment with at least two classes of chronic anti-anginal medication, of which two are at the maximally tolerated dose
• Left ventricular ejection fraction (LVEF) of ≥30%
• Not a candidate for, or unlikely to benefit from standard revascularization procedures as verified by an independent cardiologist or cardiothoracic surgeon (not a study investigator) at each center

• Can undergo ETT using the modified Bruce protocol and;

  1. ECG changes diagnostic of myocardial ischemia occur during the first 10 minutes of exercise
  2. Variability of the time to onset of ECG changes diagnostic of myocardial ischemia is ≤25% or within 60 seconds if the time to onset of myocardial ischemia occurs within the first 4 minutes of exercise as determined by two consecutive screening treadmill tests
• Evidence of stress induced myocardial ischemia by adenosine SPECT, defined as a reversible perfusion defect size of ≥9%
• Willing and able to comply with the study requirements including long-term follow-up
• Provided written informed consent

Exclusion Criteria:

• Patients of childbearing potential (must be surgically sterile or post-menopausal)
• Patients for whom an immediate revascularization procedure is indicated (CABG surgery or PCI)
• Myocardial infarction within the past 3 months
• Unstable angina or hospitalization requiring intravenous anti-anginal therapy within the 14 days prior to the start of screening evaluations
• Congestive heart failure NYHA Class IV
• Electrocardiogram that precludes accurate assessment of exercise induced myocardial ischemia (e.g., left bundle branch block, Wolf-Parkinson-White syndrome, atrial fibrillation)
• Myocarditis or restrictive pericarditis
• Left main coronary stenosis ≥70% (unless the patient has a patent graft or collateral vessels supplying the left coronary circulation) or proximal stenoses ≥70% in all major coronary conduit vessels (coronary arteries and bypass grafts)
• Clinically significant aortic or mitral valvular heart disease
• Coronary ostial stenosis that precludes adequate catheter engagement in any target vessel
• Coronary artery to venous communications, which bypass the coronary capillary bed
• Untreated life-threatening ventricular arrhythmias
• CABG surgery within the past 6 months, unless those grafts are now occluded.
• Percutaneous transluminal angioplasty (PTCA) within the past 3 months, unless the dilated vessel(s) are now occluded
• Enhanced external counterpulsation (EECP) within 3 months prior to the start of screening evaluations
• Transmyocardial or percutaneous myocardial laser revascularization within the previous year
• Prior treatment with any cardiovascular gene or stem cell therapy.
• Any intercurrent illness that may interfere with their ability to perform a maximal ETT
• Any major organ disease that substantially impairs life expectancy.
• History of cancer, other than basal cell carcinoma, or patients with any laboratory or physical exam or diagnostic procedure finding suggestive of current malignancy
• Moderate to severe nonproliferative or proliferative retinopathy from any cause (ETDRS score >35), clinically significant macular edema, or previous panretinal photocoagulation therapy
• Heparin induced thrombocytopenia or history of idiopathic thrombocytopenic purpura or other medical condition causing thrombocytopenia
• SGPT level greater than 2.0 times the upper limit of the laboratory normal range
• Bilirubin level ≥2.0 mg/dL
• Serum creatinine ≥2.5 mg/dL
• Platelet count <100,000/μL
• White blood cell count <3,000/μL
• Positive test for hepatitis B or C
• Positive test for HIV
• History of colon cancer in a first degree relative (i.e., parent, sibling or offspring) unless the patient has undergone a colonoscopy in the past 36 months with negative findings
• History of breast cancer in a first degree relative
• Patient in a family with any documented hereditary cancer syndrome
• Prior anaphylaxis reaction to iodinated contrast agents
• Patients who are known to be immunosuppressed or are receiving chronic treatment with immunosuppressive drugs
• Received an investigational drug or biologic within 30 days of screening or are currently participating in an investigational drug, biologic or device trial