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Adjunctive use of physostigmine salicylate (Anticholium®) in perioperative sepsis and septic shock: study protocol for a randomized, double-blind, placebo-controlled, monocentric trial (Anticholium® per Se).
Zimmermann, Johannes B; Pinder, Nadine; Bruckner, Thomas; Lehmann, Monika; Motsch, Johann; Brenner, Thorsten; Hoppe-Tichy, Torsten; Swoboda, Stefanie; Weigand, Markus A; Hofer, Stefan.
Afiliação
  • Zimmermann JB; Department of Anaesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. j.zimmermann@med.uni-heidelberg.de.
  • Pinder N; Department of Anaesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
  • Bruckner T; Pharmacy Department, University Hospital Heidelberg, Im Neuenheimer Feld 670, 69120, Heidelberg, Germany.
  • Lehmann M; Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.
  • Motsch J; Coordination Centre for Clinical Trials, University Hospital Heidelberg, Marsilius-Arkaden, Tower West, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.
  • Brenner T; Department of Anaesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
  • Hoppe-Tichy T; Department of Anaesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
  • Swoboda S; Pharmacy Department, University Hospital Heidelberg, Im Neuenheimer Feld 670, 69120, Heidelberg, Germany.
  • Weigand MA; Pharmacy Department, University Hospital Heidelberg, Im Neuenheimer Feld 670, 69120, Heidelberg, Germany.
  • Hofer S; Department of Anaesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
Trials ; 18(1): 530, 2017 Nov 10.
Article em En | MEDLINE | ID: mdl-29126416
ABSTRACT

BACKGROUND:

Severe sepsis and septic shock remain a major challenge, even in modern intensive care. In Germany, about 68,000 patients die annually because of septic diseases, characterized by a complex systemic inflammatory response. Causal treatment of the underlying infection is essential for successful management of sepsis, but the course can be positively influenced by supportive and adjuvant measures. The cholinergic anti-inflammatory pathway (CAP) represents a new approach to adjunctive therapy of septic diseases and can be pharmacologically activated by the acetylcholinesterase inhibitor physostigmine (Anticholium®). Promising effects can be found in several in vitro and in vivo models of sepsis, such as a reduction in pro-inflammatory cytokines and improved survival.

METHODS:

Anticholium® per Se is a randomized, double-blind, placebo-controlled, monocentric trial to assess whether the CAP can be transferred from bench to bedside. In this pilot study, 20 patients with perioperative sepsis and septic shock as a result of intra-abdominal infection are enrolled. According to randomization, participants are treated with physostigmine salicylate (verum group) or 0.9% sodium chloride (placebo group) for up to 5 days. The mean Sequential Organ Failure Assessment (SOFA) score during treatment and subsequent intensive care of up to 14 days is used as surrogate outcome (primary endpoint). Secondary outcome measures include 30- and 90-day mortality. An embedded pharmacokinetics and pharmacodynamics study investigates plasma concentrations of physostigmine and its metabolite eseroline. Further analyses will contribute to our understanding of the role of various cytokines in the pathophysiology of human sepsis. A computer-generated list is used for block randomization.

DISCUSSION:

This randomized, controlled, monocentric trial investigates for the first time the adjunctive use of physostigmine (Anticholium®) in patients with perioperative sepsis and septic shock and may be a pivotal step toward the clinical use in this indication. TRIAL REGISTRATION EudraCT Number 2012-001650-26 (entered 14 August 2012), ClinicalTrials.gov identifier NCT03013322 (registered on 1 Jan 2017).
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 4_TD / 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Fisostigmina / Choque Séptico / Inibidores da Colinesterase / Sepse / Anti-Inflamatórios Tipo de estudo: Clinical_trials / Diagnostic_studies / Guideline / Observational_studies / Prognostic_studies Limite: Aged80 País/Região como assunto: Europa Idioma: En Revista: Trials Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 4_TD / 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Fisostigmina / Choque Séptico / Inibidores da Colinesterase / Sepse / Anti-Inflamatórios Tipo de estudo: Clinical_trials / Diagnostic_studies / Guideline / Observational_studies / Prognostic_studies Limite: Aged80 País/Região como assunto: Europa Idioma: En Revista: Trials Ano de publicação: 2017 Tipo de documento: Article