Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial.
Am J Respir Crit Care Med
; 197(3): 337-347, 2018 02 01.
Article
em En
| MEDLINE
| ID: mdl-28960096
ABSTRACT
RATIONALE In septic animal models mesenchymal stem (stromal) cells (MSCs) modulate inflammation, enhance tissue repair and pathogen clearance, and reduce death. OBJECTIVES:
To conduct a phase I dose escalation trial of MSCs in septic shock with the primary objective of examining the safety and tolerability of MSCs.METHODS:
We enrolled nine participants within 24 hours of admission to the ICU. A control cohort of 21 participants was enrolled before starting the MSC interventional cohort to characterize expected adverse events (AEs) and to serve as a comparator for the intervention cohort. Three separate MSC dose cohorts, with three participants per cohort, received a single intravenous dose of 0.3, 1.0, and 3.0 × 106 cells/kg. A prespecified safety plan monitored participants for the occurrence of AEs; cytokines were collected at prespecified time points. MEASUREMENTS AND MAINRESULTS:
Ages of participants in the interventional versus observational cohorts were median of 71 (range, 38-91) and 61 (range, 23-95). Acute Physiology and Chronic Health Evaluation scores were median of 25 (range, 11-28) and 26 (range, 17-32). MSC doses ranged from 19 to 250 million cells. There were no prespecified MSC infusion-associated or serious unexpected AEs, nor any safety or efficacy signals for the expected AEs or the measured cytokines between the interventional and observational cohorts.CONCLUSIONS:
The infusion of freshly cultured allogenic bone marrow-derived MSCs, up to a dose of 3 million cells/kg (250 million cells), into participants with septic shock seems safe. Clinical trial registered with www.clinicaltrials.gov (NCT02421484).Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
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Transplante de Células-Tronco Mesenquimais
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Imunoterapia
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article