title: Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) - endotoxin removal in abdominal and urogenital septic shock with the Alteco® LPS Adsorber: study protocol for a double-blinded, randomized placebo-controlled trial.
abstract: Severe sepsis and septic shock are common in intensive care and carry high mortality rates. In patients with Gram-negative infections, early and extensive removal of endotoxin may limit the inflammatory response that characterizes septic shock. The Alteco® LPS Adsorber (hereafter referred to cited as the lipopolysaccharide (LPS) Adsorber) can be used for endotoxin removal and attenuate the deleterious inflammatory and clinical responses seen in septic shock.
  
  
  
  The Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) trial is a pilot study investigating the feasibility and safety of LPS Adsorber therapy. This pilot, multicenter, stratified, parallel, double-blinded, randomized, phase IIa, feasibility clinical investigation will be performed in five Scandinavian intensive care units. Thirty-two subjects with early septic shock and organ failure, following adequate resuscitation, will be randomized to receive either: extracorporeal veno-venous hemoperfusion therapy with the LPS Adsorber or veno-venous hemoperfusion therapy with a placebo adsorber (without active LPS-binding peptide). Patients will be stratified by infection focus such that 20 subjects with an abdominal focus (stratum A) and 12 subjects with a urogenital focus (stratum B) will be included in a parallel design. Thereafter, an interim analysis will be performed and an additional 12 patients may be included in the study. The study is designed as adaptive a priori: the patients from this study can be included in a later phase IIb study. The aim of the study is to investigate the feasibility of LPS Adsorber therapy commenced early in the time-course of septic shock. The primary endpoint will be a characterization of all reported unanticipated serious adverse device effects and anticipated serious adverse device effects. Secondary outcomes are decrease in endotoxin plasma concentration, impact on clinical outcome measures and impact on inflammatory response by LPS Adsorber therapy, as well as detailed description of the relevant mediators bound to the LPS Adsorber. Recruitment of patients will start in September 2015.
  
  
  
  The ASSET trial will give insight into the feasibility and safety of this LPS Adsorber therapy and preliminary data on its potential clinical effects in septic shock. Moreover, this pilot trial will provide with necessary data for designing future studies.
  
  
  
  ClinicalTrials.gov Identifier NCT02335723 . Registered on 28 November 2014.
authors.affiliation: Hedenstierna Laboratory, Department of Surgical Sciences/Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden. Miklos.lipcsey@surgsci.uu.se.|Department of Surgical Sciences/Anaesthesiology and Intensive Care Medicine, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden. Miklos.lipcsey@surgsci.uu.se.
authors.forename: Miklos
authors.identifier: 0000-0002-1976-4129
authors.initials: M
authors.lastname: Lipcsey
authors.affiliation: Department of Surgical Sciences/Anaesthesiology and Intensive Care Medicine, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden.
authors.forename: Jyrki
authors.initials: J
authors.lastname: Tenhunen
authors.affiliation: Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Sjölin
authors.affiliation: Department of Surgical Sciences/Anaesthesiology and Intensive Care Medicine, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Frithiof
authors.affiliation: Department of Intensive Care, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Stepani
authors.initials: S
authors.lastname: Bendel
authors.affiliation: Department of Clinical Medicine, Haukeland University Hospital, UiB, Bergen, Norway.
authors.forename: Hans
authors.initials: H
authors.lastname: Flaatten
authors.affiliation: Department of Surgical Sciences/Anaesthesiology and Intensive Care Medicine, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden.
authors.forename: Rafael
authors.initials: R
authors.lastname: Kawati
authors.affiliation: Critical Care Medicine Research Group, Tampere University Hospital, PO Box 2000, 33521, Tampere, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Kuitunen
authors.affiliation: Division of Emergencies and Critical Care, Oslo University Hospital and Institute of Clinical Medicine, 0450, Oslo, Norway.
authors.forename: Tor Inge
authors.initials: TI
authors.lastname: Tønnessen
authors.affiliation: Department of Surgical Sciences/Anaesthesiology and Intensive Care Medicine, Uppsala University, Akademiska sjukhuset, 751 85, Uppsala, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Rubertsson
mesh_terms: D000327:Adsorption; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D004311:Double-Blind Method; D005240:Feasibility Studies; D005387:Finland; D016905:Gram-Negative Bacterial Infections / Q000097:blood / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D008070:Lipopolysaccharides / Q000097:blood*; D009664:Norway; D010865:Pilot Projects; D011485:Protein Binding; D060737:Reproductive Tract Infections / Q000097:blood / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*; D012107:Research Design; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000097:blood / Q000175:diagnosis / Q000382:microbiology / Q000628:therapy*
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides
keywords: Endotoxins; Gram-negative bacteria; Hemoperfusion; Septic shock