title: A phase 2 randomized, double-blind, placebo-controlled study of the safety and efficacy of talactoferrin in patients with severe sepsis.
abstract: OBJECTIVE
  Lactoferrin is a glycoprotein with anti-infective and anti-inflammatory properties found in secretions and immune cells. Talactoferrin alfa, a recombinant form of human lactoferrin, has similar properties and plays an important role in maintaining the gastrointestinal mucosal barrier integrity. In experimental animal models, administration of talactoferrin reduces translocation of bacteria from the gut into the systemic circulation and mortality from sepsis. Our objective was to determine if talactoferrin could reduce 28-day all-cause mortality in patients with severe sepsis and to assess its safety.
  
  
  METHODS
  Prospective, randomized, double-blind, placebo-controlled, multicenter phase 2 trial.
  
  
  METHODS
  Adult ICUs and emergency departments in the United States.
  
  
  METHODS
  One hundred ninety-four adults within 24 hrs of the onset of severe sepsis.
  
  
  METHODS
  Enterally administered talactoferrin 1.5g or placebo every 8 hrs for up to 28 days or until discharge from the ICU.
  
  
  RESULTS
  Modified intention-to-treat analysis was used to assess the primary (28-day all-cause mortality) and secondary endpoints. The all-cause mortality at 28 days was 26.9% in the placebo group and 14.4% in the talactoferrin group (two-sided p = 0.052), representing a 12.5% absolute and a 46.5% relative reduction in mortality, meeting the protocol-specified primary endpoint. Reduction in all cause mortality was sustained at 6 months (p = 0.039). These reductions in mortality were observed across a wide spectrum of subgroups. The drug was well tolerated with a safety profile similar to that of placebo.
  
  
  CONCLUSIONS
  Enteral administration of talactoferrin reduced 28-day all-cause mortality in patients with severe sepsis. This reduction in mortality was sustained at 6 months. Talactoferrin was very well tolerated.
authors: Department of Medicine, Baylor College of Medicine, Ben Taub General, Hospital Houston, TX, USA. kkg@bcm.tmc.edu
authors: Kalpalatha
authors: K
authors: Guntupalli
authors: Nathan
authors: N
authors: Dean
authors: Peter E
authors: PE
authors: Morris
authors: Venkata
authors: V
authors: Bandi
authors: Benjamin
authors: B
authors: Margolis
authors: Emanuel
authors: E
authors: Rivers
authors: Mitchell
authors: M
authors: Levy
authors: Robert F
authors: RF
authors: Lodato
authors: Preeti M
authors: PM
authors: Ismail
authors: Amber
authors: A
authors: Reese
authors: John P
authors: JP
authors: Schaumberg
authors: Rajesh
authors: R
authors: Malik
authors: R Phillip
authors: RP
authors: Dellinger
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007263:Infusions, Parenteral; D007362:Intensive Care Units; D007781:Lactoferrin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; C515276:talactoferrin alfa; D007781:Lactoferrin