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

Angina Pectoris Clinical Trial

— AWARE  

Official title:

A Randomized, Double Blind, Placebo Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Ad5FGF-4 in Female Patients With Stable Angina Pectoris Who Are Not Candidates for Revascularization

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00438867
• Other study ID #: CT-3-001
• Status: Active, not recruiting
• Phase: Phase 3
• First received: February 21, 2007
• Last updated: February 11, 2013
• Start date: May 2007

Study information

• Verified date: November 2008
• Source: Cardium Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether a one-time intracoronary infusion of Ad5FGF-4 is effective in reducing the time to onset myocardial ischemia as measured by exercise treadmill testing and improving myocardial blood flow as measured by SPECT imaging. Exercise capacity, angina functional class, patient symptoms and quality of life will also be evaluated to characterize the efficacy of Ad5FGF-4. Short-term and long-term safety of Ad5FGF-4 will also be evaluated.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina Pectoris

Intervention

Genetic:
• Ad5FGF-4
Adenovirus serotype-5 mediated human fibroblast growth factor-4 gene transfer
• Placebo
Control group

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	St Joseph's Research Institute	Atlanta	Georgia
United States	Aurora Denver Cardiology	Aurora	Colorado
United States	Fox Valley Cardiovascular Consultants	Aurora	Illinois
United States	Access Clinical Trials	Beverly Hills	California
United States	University of Alabama	Birmingham	Alabama
United States	St. Luke's Idaho Cardiology Associates	Boise	Idaho
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	Heritage Cardiology Associates	Camp Hill	Pennsylvania
United States	The Lindner Clinical Trial Center	Cincinnati	Ohio
United States	Baylor University Medical Center at Dallas	Dallas	Texas
United States	Geisinger Clinic	Danville	Pennsylvania
United States	St. Mary's Duluth Clinic	Duluth	Minnesota
United States	Duke University Medical Center	Durham	North Carolina
United States	North Ohio Heart Center	Elyria	Ohio
United States	Northern Indiana Research Alliance	Fort Wayne	Indiana
United States	University of Florida	Gainesville	Florida
United States	The Stern Cardiovascular Center	Germantown	Tennessee
United States	The Care Group	Indianapolis	Indiana
United States	Mid America Heart Institute	Kansas City	Missouri
United States	BryanLGH Heart Institute	Lincoln	Nebraska
United States	South Denver Cardiology	Littleton	Colorado
United States	Midwest Heart Foundation	Lombard	Illinois
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Cardiovascular Associates	Louisville	Kentucky
United States	Minneapolis Heart Institute	Minneapolis	Minnesota
United States	Mission Internal Medical Group	Mission Viejo	California
United States	Meharry Medical College	Nashville	Tennessee
United States	Lenox Hill Heart & Vascular Institute	New York	New York
United States	Oklahoma Cardiovascular Associates	Oklahoma City	Oklahoma
United States	Creighton University	Omaha	Nebraska
United States	Florida Hospital	Orlando	Florida
United States	Banner Heart Hospital	Phoenix	Arizona
United States	Maine Medical Center	Portland	Maine
United States	Providence Heart & Vascular Institute	Portland	Oregon
United States	The Miriam Hospital	Providence	Rhode Island
United States	The Valley Hospital	Ridgewood	New Jersey
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	South Texas Cardiovascular Consultants	San Antonio	Texas
United States	UCSD Medical Center	San Diego	California
United States	Swedish Medical Center	Seattle	Washington
United States	St. Anthony's Medical Center	St. Louis	Missouri
United States	Southwest Heart	Tucson	Arizona
United States	Cardiovascular Associates of East Texas	Tyler	Texas
United States	Cardiovascular Research Institute	Washington	District of Columbia
United States	Care Foundation	Wausau	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Cardium Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in time to onset of ECG changes diagnostic of myocardial ischemia during ETT		Month 6	No
Secondary	Change in reversible perfusion defect size as measured by adenosine single-photon emission computed tomography with technetium-99m sestamibi (SPECT)(principal secondary endpoint)		Month 6	No
Secondary	Change in total exercise treadmill time		Months 3, 6 and 12	No
Secondary	Change in time to onset ECG changes diagnostic myocardial ischemia during ETT		Months 3 and 12	No
Secondary	Change in time to onset of angina during ETT		Months 3, 6 and 12	No
Secondary	Change in angina frequency and nitroglycerin		Months 3 and 6	No
Secondary	Change in patient functional status using CCS angina class		Months 3, 6 and 12	No
Secondary	Change in rest and stress left ventricular ejection fraction assessed using gated SPECT		Month 6	No
Secondary	Change in quality of life using the Seattle Angina Questionnaire		Months 6 and 12	No
Secondary	Safety of Ad5FGF-4 as assessed by adverse events and clinical laboratory testing		Through month 12	Yes
Secondary	Long-term safety of Ad5FGF-4 as assessed by clinically important events		Through month 60	Yes