Fibroblast Growth Factor-1 (FGF-1) for the Treatment of Coronary Heart Disease (ACORD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
CardioVascular BioTherapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00117936
First received: June 30, 2005
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

Treatment for no-option heart patients with coronary artery disease. Procedure includes the injection into the heart of a protein growth factor, administered by the Cordis Corp. MyoStar injection catheter, to stimulate the growth of blood vessels around blocked coronary arteries.


Condition Intervention Phase
Coronary Disease
Coronary Heart Disease
Myocardial Ischemia
Coronary Arteriosclerosis
Drug: Human Recombinant Fibroblast Growth Factor-1 (FGF 1-141)
Drug: Human Recombinant Fibroblast Growth Factor-1 (FGF1-141)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Human Recombinant Fibroblast Growth Factor-1 (FGF-1) for Intramyocardial Injection for the Treatment of Coronary Heart Disease

Resource links provided by NLM:


Further study details as provided by CardioVascular BioTherapeutics, Inc.:

Primary Outcome Measures:
  • Change in cardiac perfusion as measured by SPECT scan under stress conditions and change in vascular bed density at the sites of injections as determined by angiography [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Exercise treadmill test: time (or change in time) to onset of at least 1 mm additional horizontal or downsloping ST-segment depression, or time to ETT in the absence of at least 1 mm additional ST-segment depression due to pain (angina) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: September 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Human Recombinant Fibroblast Growth Factor-1 (FGF 1-141)
Drug: Human Recombinant Fibroblast Growth Factor-1 (FGF 1-141)
One time injection of 2 ug/kg of FGF 1-141, via a catheter
Experimental: 2
Human Recombinant Fibroblast Growth Factor-1 (FGF 1-141)
Drug: Human Recombinant Fibroblast Growth Factor-1 (FGF 1-141)
One time injection of 20 ug/kg FGF 1-141 via a catheter
Experimental: 3
Human Recombinant Fibroblast Growth Factor-1 (FGF 1-141)
Drug: Human Recombinant Fibroblast Growth Factor-1 (FGF 1-141)
One time injection of 40 ug/kg FGF 1-141, via a catheter
Placebo Comparator: 4
Human Recombinant Fibroblast Growth Factor-1 (FGF 1-141)
Drug: Human Recombinant Fibroblast Growth Factor-1 (FGF1-141)
One time injection of 0 ug/kg (placebo group), via a catheter

Detailed Description:

Patients with chronic, stable angina with documented coronary artery disease are eligible for the study.

  Eligibility

Ages Eligible for Study:   25 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Sign an informed consent form.
  2. Age ≥25 and ≤75 years, either gender, and any race.
  3. At least a 3 month history of chronic, stable angina and is relieved by rest and/or nitroglycerin.
  4. Documented symptomatic CCS Angina Classification of III to IV despite use of optimal medical therapy as noted in Inclusion Criterion 10.
  5. Pattern of CHD (coronary pathology) where percutaneous interventional therapy and/or CABG is not recommended by the treating cardiologist. This decision should have a documented basis in either complicated vessel physiology and/or lack of suitable target vessels for both PTCA and CABG, or past history of complications.
  6. One/two/three vessel disease as evidenced either by an angiographic documentation of advanced atherosclerotic narrowing of ≥60% of at least one major epicardial coronary artery (right coronary artery [RCA], left circumflex [LCX], or LAD [or any of their branches]), or of diffuse type of CHD as evidenced by the appearance on coronary angiography of multiple stenoses, multiple atherosclerotic plaques, and/or peripheral occlusion(s) of coronary vessel(s) with and without a history of MIs.
  7. demonstrate a radionuclide or angiographically determined left ventricular ejection fraction (LVEF) ≥30%.
  8. Pre-operative proof of reversible ischemia.
  9. No evidence of proliferative retinopathy or significant non-proliferative retinopathy.
  10. must be on optimal medical therapy for at least 2 months prior to entering the study, as documented by a medical history. This will include medical management, and subjects must enter the study on at least one of the following medications: beta-blockers, calcium entry blockers, ranolizine, or long-acting nitrates.
  11. Exercise duration during the qualifying treadmill tests at Visit 1 and Visit 2 is ≥3 and ≤9 minutes on a modified Bruce protocol.
  12. Exercise durations for the qualifying treadmill tests at Visits 1 and 2 must satisfy at least one of the two following conditions: (a) they differ by less than or equal to 20% of the longer time; (b) they differ by less than or equal to 60 seconds. Subjects whose ETTs at Visits 1 and 2 do not satisfy at least one of these two conditions are allowed a third ETT, at the investigator's discretion, from 5 to 7 days after Visit 2. If a third ETT is done, then when compared with the second ETT it must satisfy at least one of the two conditions above.
  13. For a treadmill test result to support inclusion it must terminate in the presence of angina for either of the following reasons: (a) angina becomes too severe to continue the test AND there must be a horizontal depression or downsloping ST-segment of at least 1 mm measured 80 ms from the J point as subsequently established by the Biomedical Systems central ECG lab, or (b) angina of any grade AND there must be a horizontal depression or downsloping ST-segment measured 80 ms from the J point of 2 mm during exercise. The qualifying time for the treadmill test will then be the time to a horizontal depression or downsloping ST-segment of 1 mm compared to the pre-exercise ST segment as subsequently established by the Biomedical Systems central ECG lab.
  14. A forced vital capacity (FVC) of ≥30%.
  15. A negative pregnancy test in women of childbearing potential at Screening.
  16. Female subjects must be post-menopausal or sterilized, or if she is of childbearing potential, she is not breast feeding, has no intention to become pregnant during the course of the study, and is using contraceptive drugs or devices.
  17. Negative cancer screening tests according to the American Cancer Society ([ACS] Appendix 13.8).
  18. Ability to complete the study in compliance with the protocol.

Exclusion criteria

  1. History of undergoing a CABG, PTCA or TMR or evidence of an acute MI in the last 3 months.
  2. Subjects with malignancies or a history of malignancies (with the exception of basal cell carcinoma [BCC] of the skin) will be excluded from the study. Those subjects with a history of BCC are eligible for enrollment, and will be monitored by a qualified dermatologist every 8 weeks for a period of 6 months for evaluation of their skin condition. Subjects with existing BCC will be excluded from the study.
  3. Evidence of concurrent clinically significant infection (e.g. elevated white blood cell [WBC] count >13,000 x 109/L, temperature >38.5°C), evidence of "common cold" or "flu."
  4. Concomitant other structural heart disease, such as moderate to severe heart valve disease, congenital heart disease, etc. other than evidence of congestive heart failure that is directly related to past ischemic events.
  5. Left ventricular thrombus (mobile or mural-based) as evidenced by ventriculogram or echocardiography.
  6. Creatine kinase (CK) levels >3 x upper limit of normal (ULN).
  7. Renal insufficiency requiring dialysis or laboratory evidence of a serum creatinine >2.0 mg/dL.
  8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x ULN.
  9. History of coagulation disorders or abnormal prothrombin time (PT) or partial thromboplastin time (PTT) >1.5 x ULN, thrombocytopenia (<100,000/µl), or ongoing anticoagulant therapy (with the exception of aspirin, up to 85 mg/day).
  10. History of blood cell diseases.
  11. Poorly controlled insulin-dependent diabetes mellitus (HbA1c >8%)
  12. Pre-existing retinal disease, including proliferative retinopathy, severe nonproliferative retinopathy.
  13. Use of any illicit recreational drugs within the past year.
  14. A positive test result for human immunodeficiency virus (HIV) antibody.
  15. Screening ECG results demonstrating recent evidence of transmural ischemia.
  16. Clinically significant ECG abnormalities, e.g.: QRS duration >0.12 seconds; QTc >450 ms in males or >460 ms in females;High-grade trioventricular (AV) block; Left bundle branch block(LBBB; Left ventricular hypertrophy(LVH) with secondary ST-T changes; Frequent, recurrent, or sustained ventricular arrhythmia; Resting ST segment depression >1 mm (measured 80 ms beyond the J point) at baseline.
  17. Subjects having a concomitant life-threatening disease in which their life expectancy is estimated to be less than 2 years.
  18. Any condition which in the opinion of the investigator would interfere with the participant's ability to provide informed consent and comply with study instructions, possibly confound interpretation of study results, or endanger the participant if he took part in the trial.
  19. Use of an investigational drug, device or product, or participation in a drug research study within a period of 30 days prior to receiving IMP.
  20. Any subject with unstable angina.
  21. Heart failure New York Heart Association (NYHA) Functional Class III or IV.
  22. Uncontrolled hypertension precluding exercise testing and/or contributing to angina severity (systolic blood pressure [SBP] >200 mmHg or diastolic blood pressure [DBP] >110 mmHg), or significant hypotension (SBP <90 mmHg or DBP <60 mmHg).
  23. Subjects currently on External Counter Pulsation therapy or who have received this therapy within 3 months prior to the screening date.
  24. Any mobility or pulmonary complication that impedes the subject's ability to perform an exercise stress test.
  25. Total fasting serum cholesterol >200 mg/dL (if levels greater than or equal to 200 mg/dL, additional medical interventions can be initiated to bring levels below 200 mg/dL).
  26. History of heparin-induced thrombocytopenia.
  27. Subjects with a history of recurrent symptomatic atrial fibrillation or significant ventricular arrhythmias.
  28. Aortic or mitral valve replacement.
  29. Subjects who have undergone heart transplantation.
  30. Medical history and physical examination displaying any evidence that catheterization is contraindicated.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00117936

Locations
United States, Alabama
Princeton Baptist Medical Center
Birmingham, Alabama, United States, 35211
United States, Arizona
Mercy Gilbert Medical Center
Gilbert, Arizona, United States, 85297
United States, California
Medical Center, University of California, San Diego
San Diego, California, United States, 92103
United States, Florida
Jim Moran Heart and Vascular Research Institute
Ft. Lauderdale, Florida, United States, 33308
Florida Hospital and Cardiovascular Institute
Orlando, Florida, United States, 32801
United States, Illinois
Cardiac Catheterization Labs, Rush Univ Medical Center
Chicago, Illinois, United States, 60612
United States, Minnesota
Minneapolis Heart Institute Foundation
Minneapolis, Minnesota, United States, 55407
United States, Ohio
Fairfield Cardiac Cath Lab
Cincinnati, Ohio, United States, 45219
University of Cincinnati
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
CardioVascular BioTherapeutics, Inc.
Investigators
Principal Investigator: Nabil Dib, MD Mercy Gilbert Medical Center, Gilbert Az.
  More Information

Additional Information:
No publications provided

Responsible Party: CardioVascular BioTherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT00117936     History of Changes
Obsolete Identifiers: NCT00032318
Other Study ID Numbers: CVBT-CHD07-01
Study First Received: June 30, 2005
Last Updated: August 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by CardioVascular BioTherapeutics, Inc.:
Angiogenesis
No-option heart patients
Blocked coronary artery
Revascularization
FGF-1
growth factor

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Arteriosclerosis
Atherosclerosis
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014