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1.
Contemp Clin Trials ; 91: 105975, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32145440

RESUMO

BACKGROUND: Lower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promising results in experimental models and phase I/IIA clinical trials. The GPAD-3 trial will study the effect of two successive administrations of GM-CSF at 3-month interval for improving claudication among patients with lower extremity PAD. METHODS: We plan to recruit 176 patients in this ongoing randomized, double-blind, placebo-controlled Phase IIB trial. After screening for inclusion and exclusion criteria, eligible subjects undergo a 4-week screening phase where they perform subcutaneous placebo injections thrice weekly and walk at least three times a day until they develop claudication. After the screening phase, eligible subjects undergo baseline testing and are randomized 2:1 to receive 500 µg/day of GM-CSF subcutaneously thrice weekly for three weeks or placebo injections. After 3 months, follow-up endpoint testing is performed and subjects in the GM-CSF group receive the second administration of the drug for three weeks while subjects in placebo group receive matching placebo injections. All participants undergo endpoint testing at six-month and nine-month follow-up. The primary endpoint is change in 6-min walk distance between baseline and 6-month follow-up. CONCLUSION: GPAD-3 explores a novel approach to address the need for alternative therapies that can alleviate symptoms among patients with lower extremity PAD. If successful, this study will pave the way for a pivotal Phase III trial.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Extremidade Inferior , Doença Arterial Periférica/terapia , Índice Tornozelo-Braço , Diabetes Mellitus/epidemiologia , Método Duplo-Cego , Teste de Esforço , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Humanos , Injeções Subcutâneas , Masculino , Doença Arterial Periférica/epidemiologia , Caminhada/fisiologia
2.
Circ Res ; 120(2): 324-331, 2017 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-27821724

RESUMO

RATIONALE: Despite direct immediate intervention and therapy, ST-segment-elevation myocardial infarction (STEMI) victims remain at risk for infarct expansion, heart failure, reinfarction, repeat revascularization, and death. OBJECTIVE: To evaluate the safety and bioactivity of autologous CD34+ cell (CLBS10) intracoronary infusion in patients with left ventricular dysfunction post STEMI. METHODS AND RESULTS: Patients who underwent successful stenting for STEMI and had left ventricular dysfunction (ejection fraction≤48%) ≥4 days poststent were eligible for enrollment. Subjects (N=161) underwent mini bone marrow harvest and were randomized 1:1 to receive (1) autologous CD34+ cells (minimum 10 mol/L±20% cells; N=78) or (2) diluent alone (N=83), via intracoronary infusion. The primary safety end point was adverse events, serious adverse events, and major adverse cardiac event. The primary efficacy end point was change in resting myocardial perfusion over 6 months. No differences in myocardial perfusion or adverse events were observed between the control and treatment groups, although increased perfusion was observed within each group from baseline to 6 months (P<0.001). In secondary analyses, when adjusted for time of ischemia, a consistently favorable cell dose-dependent effect was observed in the change in left ventricular ejection fraction and infarct size, and the duration of time subjects was alive and out of hospital (P=0.05). At 1 year, 3.6% (N=3) and 0% deaths were observed in the control and treatment group, respectively. CONCLUSIONS: This PreSERVE-AMI (Phase 2, randomized, double-blind, placebo-controlled trial) represents the largest study of cell-based therapy for STEMI completed in the United States and provides evidence supporting safety and potential efficacy in patients with left ventricular dysfunction post STEMI who are at risk for death and major morbidity. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01495364.


Assuntos
Antígenos CD34/administração & dosagem , Transplante de Medula Óssea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/terapia , Idoso , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Infusões Intra-Arteriais/métodos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Transplante Autólogo/métodos , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia
3.
JACC Basic Transl Sci ; 1(7): 576-586, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30167542

RESUMO

A first-in-human, phase 1, double blind, placebo-controlled, single ascending dose study examined the safety, tolerability, and exploratory efficacy of intravenous infusion of a recombinant growth factor, cimaglermin alfa, in patients with heart failure and left ventricular systolic dysfunction (LVSD). In these patients on optimal guideline-directed medical therapy, cimaglermin treatment was generally tolerated except for transient nausea and headache and a dose-limiting toxicity was noted at the highest planned dose. There was a dose-dependent improvement in left ventricular ejection fraction lasting 90 days following infusion. Thus, cimaglermin is a potential therapy to enhance cardiac function in LVSD and warrants further investigation.

4.
Curr Atheroscler Rep ; 13(5): 396-404, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21830102

RESUMO

Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are inadequate to identify the asymptomatic high-risk individuals. Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would allow the early adoption of aggressive preventative interventions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively simple and inexpensive genetic markers of increased CHD risk can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite nominal cost and radiation exposure. Additionally, genetic markers are fixed and need only be measured once in a patient's lifetime, can help guide therapy selection, and may be of utility in family counseling.


Assuntos
Doença das Coronárias/genética , Doença das Coronárias/terapia , Testes Genéticos , Alelos , Diagnóstico por Imagem , Diagnóstico Precoce , Genótipo , Humanos , Programas de Rastreamento , Fenótipo , Polimorfismo Genético , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco
5.
Am J Cardiol ; 99(11): 1529-34, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17531575

RESUMO

This study prospectively evaluated the diagnostic accuracy of 64-slice computed tomographic angiography (CTA) in assessing the patency of coronary artery bypass grafts compared with invasive coronary angiography. In total 147 bypass grafts (100 venous grafts and 47 mammary artery grafts) were evaluated in 50 consecutive patients. Contrast-enhanced 64-slice CTA was performed and compared with invasive angiography. The computed tomographic angiographic scan protocol used 64- x 0.5-mm slice collimation and 0.33-second gantry rotation time during simultaneous electrocardiographic gating. Patients with a heart rate >65 beats/min received beta blockers. Overall 145 of 147 bypass grafts (98.6%) were detected by CTA; 2 nonvisualized grafts were occluded at the time of invasive angiography. Of the grafts visualized, 28 were totally occluded, 103 were patent, and 14 had significant stenoses that were confirmed by invasive angiography. Ninety-five percent (111 of 117) of patent grafts demonstrated good run-off distal to anastomoses but without an ability to accurately evaluate the presence of retrograde flow; 83% (97 of 117) of distal anastomoses were adequately evaluated, whereas the remaining 17% (20 of 117) were not well visualized due to vascular clips and/or calcification artifacts. Two grafts were not demonstrated by invasive angiography but were detected by CTA and found to be widely patent. In conclusion, multidetector 64-slice CTA is a valuable tool for direct visualization of coronary bypass grafts and assessment of their patency. Dysfunctional bypass grafts can be detected with high diagnostic accuracy.


Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Tomografia Computadorizada por Raios X , Grau de Desobstrução Vascular , Idoso , Inteligência Artificial , Circulação Coronária , Estenose Coronária/epidemiologia , Estenose Coronária/cirurgia , Estudos Transversais , Eletrocardiografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
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