title: Talactoferrin in Severe Sepsis: Results From the Phase II/III Oral tAlactoferrin in Severe sepsIS Trial.
abstract: OBJECTIVE
  Talactoferrin alfa is a recombinant form of the human glycoprotein, lactoferrin, which has been shown to have a wide range of effects on the immune system. This phase II/III clinical trial compared talactoferrin with placebo, in addition to standard of care, in patients with severe sepsis.
  
  
  METHODS
  Multicenter, randomized, placebo-controlled, phase II/III clinical study.
  
  
  METHODS
  Seventy-seven centers in 10 countries.
  
  
  METHODS
  Adult (> 18 yr) patients admitted to one of the participating centers with severe sepsis who were receiving antimicrobial therapy and able to take liquid medication by mouth or feeding tube.
  
  
  METHODS
  Patients were randomized to receive either talactoferrin (1.5 g, 15 mL) or placebo three times a day orally or by another enteral route for 28 days or until ICU discharge.
  
  
  RESULTS
  The study was terminated after 305 patients had been enrolled (153 talactoferrin and 152 placebo) because of futility and safety concerns identified by the Data Safety Monitoring Board. There were no significant differences between groups in baseline characteristics including age, sex, site of infection, and severity scores. Twenty-eight-day mortality was higher in talactoferrin-treated patients although this difference was not statistically significant (24.8% vs 17.8% placebo; p = 0.117). The difference was largely the result of differences in patients with shock (talactoferrin, 33/105 [31.4%] vs placebo, 21/104 [20.2%]; p = 0.064); no mortality difference was seen in patients without shock (talactoferrin, 5/48 [10.4%] vs placebo, 6/48 [12.5%]; p = 0.806). In-hospital (43/153 [28.1%] vs 27/152 [17.8%]; p = 0.037) and 3-month (46/153 [30.1%] vs 31/152 [20.4%]; p = 0.036) mortality rates were significantly higher in talactoferrin-treated patients than in patients in the placebo group. The occurrence of treatment-related adverse or serious adverse events was similar between groups.
  
  
  CONCLUSIONS
  Administration of oral talactoferrin was not associated with reduced 28-day mortality in patients with severe sepsis and may even be harmful.
authors.affiliation: 1Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussels, Belgium. 2Department of Surgery, Interdepartmental Division of Critical Care Medicine, University of Toronto, St. Michael's Hospital, Toronto, ON, Canada. 3Department of Medicine, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, NJ. 4Discovery Laboratories, Warrington, PA. 5Pulmonary Critical Care and Sleep Section, Department of Medicine, Baylor College of Medicine, Houston, TX. 6Warren Alpert Medical School at Brown University, Rhode Island Hospital, Providence, RI. 7Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom. 8Agennix, Princeton, NJ.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.forename: R Phillip
authors.initials: RP
authors.lastname: Dellinger
authors.forename: Steven G
authors.initials: SG
authors.lastname: Simonson
authors.forename: Kalpalatha
authors.initials: K
authors.lastname: Guntupalli
authors.forename: Mitchell M
authors.initials: MM
authors.lastname: Levy
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
authors.forename: Rajesh
authors.initials: R
authors.lastname: Malik
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007781:Lactoferrin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality*; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality
chemical_list: D000890:Anti-Infective Agents; C515276:talactoferrin alfa; D007781:Lactoferrin