Clinical trial NCT00438867: Angiogenesis in Women With Angina Pectoris Who Are Not Candidates for Revascularization
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Angina Pectoris
Keywords: angina
FGF-4
angiogenesis
growth factor
myocardia ischemia
revascularization
Lead sponsor: Cardium Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-02-22
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in time to onset of ECG changes diagnostic of myocardial ischemia during ETT
timeFrame: Month 6
Secondary outcomes:
measure: Change in reversible perfusion defect size as measured by adenosine single-photon emission computed tomography with technetium-99m sestamibi (SPECT)(principal secondary endpoint)
timeFrame: Month 6
measure: Change in total exercise treadmill time
timeFrame: Months 3, 6 and 12
measure: Change in time to onset ECG changes diagnostic myocardial ischemia during ETT
timeFrame: Months 3 and 12
measure: Change in time to onset of angina during ETT
timeFrame: Months 3, 6 and 12
measure: Change in angina frequency and nitroglycerin
timeFrame: Months 3 and 6
measure: Change in patient functional status using CCS angina class
timeFrame: Months 3, 6 and 12
measure: Change in rest and stress left ventricular ejection fraction assessed using gated SPECT
timeFrame: Month 6
measure: Change in quality of life using the Seattle Angina Questionnaire
timeFrame: Months 6 and 12
measure: Safety of Ad5FGF-4 as assessed by adverse events and clinical laboratory testing
timeFrame: Through month 12
measure: Long-term safety of Ad5FGF-4 as assessed by clinically important events
timeFrame: Through month 60
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Banner Heart Hospital
state: Arizona
city: Tucson
country: United States
facility: Southwest Heart
state: Arizona
city: Beverly Hills
country: United States
facility: Access Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Mission Viejo
country: United States
facility: Mission Internal Medical Group
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: Aurora
country: United States
facility: Aurora Denver Cardiology
state: Colorado
city: Littleton
country: United States
facility: South Denver Cardiology
state: Colorado
city: Washington
country: United States
facility: Cardiovascular Research Institute
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: St Joseph's Research Institute
state: Georgia
city: Boise
country: United States
facility: St. Luke's Idaho Cardiology Associates
state: Idaho
city: Aurora
country: United States
facility: Fox Valley Cardiovascular Consultants
state: Illinois
city: Lombard
country: United States
facility: Midwest Heart Foundation
state: Illinois
city: Fort Wayne
country: United States
facility: Northern Indiana Research Alliance
state: Indiana
city: Indianapolis
country: United States
facility: The Care Group
state: Indiana
city: Louisville
country: United States
facility: Cardiovascular Associates
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Duluth
country: United States
facility: St. Mary's Duluth Clinic
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Kansas City
country: United States
facility: Mid America Heart Institute
state: Missouri
city: St. Louis
country: United States
facility: St. Anthony's Medical Center
state: Missouri
city: Lincoln
country: United States
facility: BryanLGH Heart Institute
state: Nebraska
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: New York
country: United States
facility: Lenox Hill Heart & Vascular Institute
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Elyria
country: United States
facility: North Ohio Heart Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Cardiovascular Associates
state: Oklahoma
city: Portland
country: United States
facility: Providence Heart & Vascular Institute
state: Oregon
city: Camp Hill
country: United States
facility: Heritage Cardiology Associates
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Germantown
country: United States
facility: The Stern Cardiovascular Center
state: Tennessee
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center at Dallas
state: Texas
city: San Antonio
country: United States
facility: South Texas Cardiovascular Consultants
state: Texas
city: Tyler
country: United States
facility: Cardiovascular Associates of East Texas
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Wausau
country: United States
facility: Care Foundation
state: Wisconsin
Study officials:
affiliation: Cardium Therapeutics
name: Robert Engler, MD
role: STUDY_DIRECTOR
References:
citation: Henry TD, Grines CL, Watkins MW, Dib N, Barbeau G, Moreadith R, Andrasfay T, Engler RL. Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials. J Am Coll Cardiol. 2007 Sep 11;50(11):1038-46. doi: 10.1016/j.jacc.2007.06.010. Epub 2007 Aug 24.