Angiogenesis Using VEGF-A165/bFGF Plasmid Delivered Percutaneously in No-option CAD Patients; a Controlled Trial

NCT00620217 | Completed Phase 2 DMC

• 1 other identifier: PBZ-KBN-099/P05/01
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Achieving therapeutic angiogenesis with gene therapy using a plasmid coding human VEGF-A165/bFGF injected into ischemic myocardium of refractory coronary artery disease patients, employing a percutaneous catheter-based technique- a double-blind placebo controlled study. Some patients with persistent coronary artery disease cannot be effectively treated using methods available today ("no-option" patients). It is currently evident that an emerging therapy for them might be the stimulation of neoangiogenesis in the area of ischemic myocardium using growth factor genes. Agents attracting greatest interest are FGF (fibroblast growth factor) and VEGF (vascular-endothelial growth factor). A number of methods have been tested to deliver these agents to the area of interest. Basic research has revealed that potent forms of angiogenic growth factors are the basic FGF (bFGF) and VEGF type A. Most clinical research on therapeutic angiogenesis is done using one of these two growth factors. This is to our knowledge the first clinical study using bicistronic VEGF-A 165/bFGF plasmid. Patient population will comprise CCS III and CCS IV coronary artery disease patients who cannot be treated with standard revascularization methods. In the course of study we shall attempt to analyze the efficacy of therapeutic plasmid-induced angiogenesis in terms of myocardial perfusion increase and clinical symptom improvement. The feasibility and safety of plasmid delivery method will also be assessed. A percutaneous catheter-based technique (Myo-Star, Johnson \& Johnson®) is used for plasmid delivery. All patients enrolled will receive optimal medical treatment as judged by treating physician. An effort will be made to modify medical therapy during the study course only for clear reasons. Standard angiography and ventriculography will be performed prior to plasmid injection therapy. Ischemic area of interest will be identified on inclusion by SPECT. Cardiac nuclear magnetic resonance (cNMR) with adenosine will also be performed to assess heart morphology, function and perfusion. Next, injections will be performed according to protocol. Follow-up visits will be performed at month 4 and month 12 after injection therapy. A change in myocardial perfusion at rest and on dipyridamole-stress SPECT evaluation after injection therapy will be the primary measure of efficacy. Changes in exercise tolerance will also be monitored along with a number of other efficacy and safety parameters.

Conditions

Coronary Artery Disease

Keywords

heart ischemia; coronary artery disease; plasmid; VEGF; FGF; percutaneous; gene therapy; SPECT; nuclear magnetic resonance

Outcome Measures

Primary Outcomes (1)

• Change in myocardial perfusion at rest and on dipyridamole-stress SPECT evaluation at month 4 after injection therapy

  4 months

Secondary Outcomes (7)

• Changes in exercise tolerance

  month 4 and 12

• Changes in life quality and patient's clinical condition

  month 4 and 12

• Angiographic changes

  4 months

• The occurrence of major cardiac adverse events (MACE) during long-term follow-up

  throughout the 1-year follow-up

• Serum VEGF-A165 and bFGF level

  week 1,2,4,8

Study Arms (2)

1

EXPERIMENTAL

intramyocardial injection of bicistronic VEGF-A165/bFGF plasmid

Genetic: intramyocardial injection of VEGF-A165/bFGF:placebo plasmid

2

PLACEBO COMPARATOR

intramyocardial injection of placebo plasmid

Genetic: intramyocardial injection of VEGF-A165/bFGF:placebo plasmid

Interventions

intramyocardial injection of VEGF-A165/bFGF:placebo plasmid GENETIC

The plasmid will be given at a total dose of 0.5 mg, 10 injections of 0,2 ml each into the region of reversible ischemia. The process of injecting the solution into each of ten points within the ischemic zone will take 20 to 40 seconds to minimize muscle disruption

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe (\>= CCS III) ischemic heart disease despite optimal medical treatment in patients not amenable to percutaneous transluminal coronary angioplasty or coronary artery bypass surgery
• Left ventricular ejection fraction \>35%
• Significant stress-induced reversible ischemic area documented on dipyridamole stress myocardial perfusion scintigraphy
• Able to understand and willing to sign the informed consent
• Older than 18 years of age

You may not qualify if:

• Angina \<CCS III
• Secondary angina
• Diabetes with proliferative retinopathy
• Diagnosed or suspected tumor
• Chronic inflammatory or autoimmune disease
• Fertile women
• Left ventricular ejection fraction \<35%
• Patients not willing to or not able to give the informed consent to participate in the study
• Patients with a severe disease (other than CAD) having life-expectancy below 1 year

Sponsors & Collaborators

• National Institute of Cardiology, Warsaw, Poland: lead
• Center of Oncology, Warsaw, Poland: collaborator
• Medical University of Warsaw: collaborator
• Ministry of Scientific Research and Information Technology, Poland: collaborator
• Polpharma Foundation for Development of Polish Pharmacy and Medicine: collaborator

Study Sites (1)

Institute of Cardiology

Warsaw, 04-628, Poland

Location

Related Publications (3)

• Kukula, K., Dabrowski, M., Chojnowska, L., Chmielak, Z., Witkowski, A., Skwarek, M., Kadziela, J., Malecki, M., Teresinska, A., Kownacki, L., Piotrowska-Kownacka, D., Ruzyllo, W., Theoretical base and investigational plan of the VIFCAD study- gene therapy for refractory coronary artery disease in no-option patients using transendocardial bicistronic VEGF/FGF plasmid injection. Post Kardiol Interw; 2, 1 (2006) 116-123

  BACKGROUND

• Kukula K, Urbanowicz A, Klopotowski M, Dabrowski M, Pregowski J, Kadziela J, Chmielak Z, Witkowski A, Ruzyllo W. Long-term follow-up and safety assessment of angiogenic gene therapy trial VIF-CAD: Transcatheter intramyocardial administration of a bicistronic plasmid expressing VEGF-A165/bFGF cDNA for the treatment of refractory coronary artery disease. Am Heart J. 2019 Sep;215:78-82. doi: 10.1016/j.ahj.2019.06.009. Epub 2019 Jun 19.

  PMID: 31288177 DERIVED

• Kukula K, Chojnowska L, Dabrowski M, Witkowski A, Chmielak Z, Skwarek M, Kadziela J, Teresinska A, Malecki M, Janik P, Lewandowski Z, Klopotowski M, Wnuk J, Ruzyllo W. Intramyocardial plasmid-encoding human vascular endothelial growth factor A165/basic fibroblast growth factor therapy using percutaneous transcatheter approach in patients with refractory coronary artery disease (VIF-CAD). Am Heart J. 2011 Mar;161(3):581-9. doi: 10.1016/j.ahj.2010.11.023. Epub 2011 Jan 31.

  PMID: 21392615 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Witold Ruzyllo, Prof.

  National Institute of Cardiology, Warsaw, Poland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 4, 2008
• First Posted: February 21, 2008
• Study Start: December 1, 2004
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2009
• Last Updated: December 1, 2009

Record last verified: 2009-11

Locations

PL (1)