High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial

Autores
Favaloro, Liliana; Diez, Mirta; Mendiz, Oscar; Vera Janavel, Gustavo; Valdivieso, León; Ratto, Roxana; Garelli, Guillermo; Salmo, Fabián; Criscuolo, Marcelo; Bercovich, Andrés; Crottogini, Alberto Jose
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: We aimed to assess safety and, secondarily, the efficacy of intramyocardial high-dose plasmid-vascular endothelial growth factor (VEGF) 165 (pVEGF165) gene transfer in no-option patients with coronary artery disease (CAD). Background: Controlled trials of pVEGF165 in CAD have shown little benefit. One possible reason is shortness of dosage. We have shown in large mammalian models of chronic myocardial ischemia and acute myocardial infarction that intramyocardial pVEGF165 at doses significantly higher than those used in recent phase II trials is safe and efficacious on myocardial perfusion, left ventricular function, and infarct size limitation. Methods: Using an injection catheter, 10 patients with severe CAD not amenable for revascularization received 10 intramyocardial injections of 0.38 mg (total dose, 3.8 mg) pVEGF165 in zones exhibiting myocardial ischemia, as assessed by combined stress 99mTc-sestamibi single-photon emission computed tomography and stress echocardiography. Results: No serious adverse events related to either VEGF or the injection procedure occurred over the 2-year follow-up. One patient suffered femoral artery thrombosis after a follow-up coronary angiography, successfully resolved with medical treatment. Six patients suffered uncomplicated coronary ischemic events during the second year follow-up. Angina functional class decreased from 2.6 6 0.2 to 1.2 6 0.3 (mean 6 SEM, P < 0.05), quality of life increased from 56.9 6 3.2 to 82.6 6 2.4 (P < 0.05), the summed difference score of myocardial perfusion decreased from 13.4 6 2 to 7.7 6 1.8 (P < 0.04), and stress ejection fraction did not change (44.2 6 3.6% to 47.8 6 3.1%, P 5 NS). Conclusions: High-dose intramyocardial pVEGF165 is safe at 2 years follow-up in patients with severe CAD. The efficacy results observed must be taken cautiously given the uncontrolled, open-label study design.
Fil: Favaloro, Liliana. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Diez, Mirta. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Mendiz, Oscar. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Vera Janavel, Gustavo. Universidad Favaloro; Argentina. Bio-sidus S.a.; Argentina
Fil: Valdivieso, León. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Ratto, Roxana. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Garelli, Guillermo. Biosidus S. A.; Argentina
Fil: Salmo, Fabián. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Criscuolo, Marcelo. Biosidus S. A.; Argentina
Fil: Bercovich, Andrés. Biosidus S. A.; Argentina
Fil: Crottogini, Alberto Jose. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Angiogenesis
Gene Therapy
Myocardial Ischemia
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/12317
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/12317
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up TrialFavaloro, LilianaDiez, MirtaMendiz, OscarVera Janavel, GustavoValdivieso, LeónRatto, RoxanaGarelli, GuillermoSalmo, FabiánCriscuolo, MarceloBercovich, AndrésCrottogini, Alberto JoseAngiogenesisGene TherapyMyocardial Ischemiahttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objectives: We aimed to assess safety and, secondarily, the efficacy of intramyocardial high-dose plasmid-vascular endothelial growth factor (VEGF) 165 (pVEGF165) gene transfer in no-option patients with coronary artery disease (CAD). Background: Controlled trials of pVEGF165 in CAD have shown little benefit. One possible reason is shortness of dosage. We have shown in large mammalian models of chronic myocardial ischemia and acute myocardial infarction that intramyocardial pVEGF165 at doses significantly higher than those used in recent phase II trials is safe and efficacious on myocardial perfusion, left ventricular function, and infarct size limitation. Methods: Using an injection catheter, 10 patients with severe CAD not amenable for revascularization received 10 intramyocardial injections of 0.38 mg (total dose, 3.8 mg) pVEGF165 in zones exhibiting myocardial ischemia, as assessed by combined stress 99mTc-sestamibi single-photon emission computed tomography and stress echocardiography. Results: No serious adverse events related to either VEGF or the injection procedure occurred over the 2-year follow-up. One patient suffered femoral artery thrombosis after a follow-up coronary angiography, successfully resolved with medical treatment. Six patients suffered uncomplicated coronary ischemic events during the second year follow-up. Angina functional class decreased from 2.6 6 0.2 to 1.2 6 0.3 (mean 6 SEM, P < 0.05), quality of life increased from 56.9 6 3.2 to 82.6 6 2.4 (P < 0.05), the summed difference score of myocardial perfusion decreased from 13.4 6 2 to 7.7 6 1.8 (P < 0.04), and stress ejection fraction did not change (44.2 6 3.6% to 47.8 6 3.1%, P 5 NS). Conclusions: High-dose intramyocardial pVEGF165 is safe at 2 years follow-up in patients with severe CAD. The efficacy results observed must be taken cautiously given the uncontrolled, open-label study design.Fil: Favaloro, Liliana. Fundacion Favaloro; Argentina. Universidad Favaloro; ArgentinaFil: Diez, Mirta. Fundacion Favaloro; Argentina. Universidad Favaloro; ArgentinaFil: Mendiz, Oscar. Fundacion Favaloro; Argentina. Universidad Favaloro; ArgentinaFil: Vera Janavel, Gustavo. Universidad Favaloro; Argentina. Bio-sidus S.a.; ArgentinaFil: Valdivieso, León. Fundacion Favaloro; Argentina. Universidad Favaloro; ArgentinaFil: Ratto, Roxana. Fundacion Favaloro; Argentina. Universidad Favaloro; ArgentinaFil: Garelli, Guillermo. Biosidus S. A.; ArgentinaFil: Salmo, Fabián. Fundacion Favaloro; Argentina. Universidad Favaloro; ArgentinaFil: Criscuolo, Marcelo. Biosidus S. A.; ArgentinaFil: Bercovich, Andrés. Biosidus S. A.; ArgentinaFil: Crottogini, Alberto Jose. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaWiley2013-11-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12317Favaloro, Liliana; Diez, Mirta; Mendiz, Oscar; Vera Janavel, Gustavo; Valdivieso, León; et al.; High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial; Wiley; Catheterization And Cardiovascular Interventions : Official Journal Of The Society For Cardiac Angiography & Interventions.; 82; 6; 15-11-2013; 899-9061522-19461522-726Xenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/ccd.24555/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1002/ccd.24555info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:36:50Zoai:ri.conicet.gov.ar:11336/12317instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:36:50.581CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial
title High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial
spellingShingle High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial
Favaloro, Liliana
Angiogenesis
Gene Therapy
Myocardial Ischemia
title_short High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial
title_full High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial
title_fullStr High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial
title_full_unstemmed High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial
title_sort High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial
dc.creator.none.fl_str_mv Favaloro, Liliana
Diez, Mirta
Mendiz, Oscar
Vera Janavel, Gustavo
Valdivieso, León
Ratto, Roxana
Garelli, Guillermo
Salmo, Fabián
Criscuolo, Marcelo
Bercovich, Andrés
Crottogini, Alberto Jose
author Favaloro, Liliana
author_facet Favaloro, Liliana
Diez, Mirta
Mendiz, Oscar
Vera Janavel, Gustavo
Valdivieso, León
Ratto, Roxana
Garelli, Guillermo
Salmo, Fabián
Criscuolo, Marcelo
Bercovich, Andrés
Crottogini, Alberto Jose
author_role author
author2 Diez, Mirta
Mendiz, Oscar
Vera Janavel, Gustavo
Valdivieso, León
Ratto, Roxana
Garelli, Guillermo
Salmo, Fabián
Criscuolo, Marcelo
Bercovich, Andrés
Crottogini, Alberto Jose
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Angiogenesis
Gene Therapy
Myocardial Ischemia
topic Angiogenesis
Gene Therapy
Myocardial Ischemia
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objectives: We aimed to assess safety and, secondarily, the efficacy of intramyocardial high-dose plasmid-vascular endothelial growth factor (VEGF) 165 (pVEGF165) gene transfer in no-option patients with coronary artery disease (CAD). Background: Controlled trials of pVEGF165 in CAD have shown little benefit. One possible reason is shortness of dosage. We have shown in large mammalian models of chronic myocardial ischemia and acute myocardial infarction that intramyocardial pVEGF165 at doses significantly higher than those used in recent phase II trials is safe and efficacious on myocardial perfusion, left ventricular function, and infarct size limitation. Methods: Using an injection catheter, 10 patients with severe CAD not amenable for revascularization received 10 intramyocardial injections of 0.38 mg (total dose, 3.8 mg) pVEGF165 in zones exhibiting myocardial ischemia, as assessed by combined stress 99mTc-sestamibi single-photon emission computed tomography and stress echocardiography. Results: No serious adverse events related to either VEGF or the injection procedure occurred over the 2-year follow-up. One patient suffered femoral artery thrombosis after a follow-up coronary angiography, successfully resolved with medical treatment. Six patients suffered uncomplicated coronary ischemic events during the second year follow-up. Angina functional class decreased from 2.6 6 0.2 to 1.2 6 0.3 (mean 6 SEM, P < 0.05), quality of life increased from 56.9 6 3.2 to 82.6 6 2.4 (P < 0.05), the summed difference score of myocardial perfusion decreased from 13.4 6 2 to 7.7 6 1.8 (P < 0.04), and stress ejection fraction did not change (44.2 6 3.6% to 47.8 6 3.1%, P 5 NS). Conclusions: High-dose intramyocardial pVEGF165 is safe at 2 years follow-up in patients with severe CAD. The efficacy results observed must be taken cautiously given the uncontrolled, open-label study design.
Fil: Favaloro, Liliana. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Diez, Mirta. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Mendiz, Oscar. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Vera Janavel, Gustavo. Universidad Favaloro; Argentina. Bio-sidus S.a.; Argentina
Fil: Valdivieso, León. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Ratto, Roxana. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Garelli, Guillermo. Biosidus S. A.; Argentina
Fil: Salmo, Fabián. Fundacion Favaloro; Argentina. Universidad Favaloro; Argentina
Fil: Criscuolo, Marcelo. Biosidus S. A.; Argentina
Fil: Bercovich, Andrés. Biosidus S. A.; Argentina
Fil: Crottogini, Alberto Jose. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Objectives: We aimed to assess safety and, secondarily, the efficacy of intramyocardial high-dose plasmid-vascular endothelial growth factor (VEGF) 165 (pVEGF165) gene transfer in no-option patients with coronary artery disease (CAD). Background: Controlled trials of pVEGF165 in CAD have shown little benefit. One possible reason is shortness of dosage. We have shown in large mammalian models of chronic myocardial ischemia and acute myocardial infarction that intramyocardial pVEGF165 at doses significantly higher than those used in recent phase II trials is safe and efficacious on myocardial perfusion, left ventricular function, and infarct size limitation. Methods: Using an injection catheter, 10 patients with severe CAD not amenable for revascularization received 10 intramyocardial injections of 0.38 mg (total dose, 3.8 mg) pVEGF165 in zones exhibiting myocardial ischemia, as assessed by combined stress 99mTc-sestamibi single-photon emission computed tomography and stress echocardiography. Results: No serious adverse events related to either VEGF or the injection procedure occurred over the 2-year follow-up. One patient suffered femoral artery thrombosis after a follow-up coronary angiography, successfully resolved with medical treatment. Six patients suffered uncomplicated coronary ischemic events during the second year follow-up. Angina functional class decreased from 2.6 6 0.2 to 1.2 6 0.3 (mean 6 SEM, P < 0.05), quality of life increased from 56.9 6 3.2 to 82.6 6 2.4 (P < 0.05), the summed difference score of myocardial perfusion decreased from 13.4 6 2 to 7.7 6 1.8 (P < 0.04), and stress ejection fraction did not change (44.2 6 3.6% to 47.8 6 3.1%, P 5 NS). Conclusions: High-dose intramyocardial pVEGF165 is safe at 2 years follow-up in patients with severe CAD. The efficacy results observed must be taken cautiously given the uncontrolled, open-label study design.
publishDate 2013
dc.date.none.fl_str_mv 2013-11-15
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/12317
Favaloro, Liliana; Diez, Mirta; Mendiz, Oscar; Vera Janavel, Gustavo; Valdivieso, León; et al.; High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial; Wiley; Catheterization And Cardiovascular Interventions : Official Journal Of The Society For Cardiac Angiography & Interventions.; 82; 6; 15-11-2013; 899-906
1522-1946
1522-726X
url http://hdl.handle.net/11336/12317
identifier_str_mv Favaloro, Liliana; Diez, Mirta; Mendiz, Oscar; Vera Janavel, Gustavo; Valdivieso, León; et al.; High-Dose Plasmid-Mediated VEGF Gene Transfer is Safe in Patients With Severe Ischemic Heart Disease (GENESIS-I): A Phase I, Open-Label, Two-Year Follow-up Trial; Wiley; Catheterization And Cardiovascular Interventions : Official Journal Of The Society For Cardiac Angiography & Interventions.; 82; 6; 15-11-2013; 899-906
1522-1946
1522-726X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/ccd.24555/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1002/ccd.24555
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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