TY - JOUR
T1 - A phase 2 randomized, double-blind, placebo-controlled study of the safety and efficacy of talactoferrin in patients with severe sepsis
AU - Guntupalli, Kalpalatha
AU - Dean, Nathan
AU - Morris, Peter E.
AU - Bandi, Venkata
AU - Margolis, Benjamin
AU - Rivers, Emanuel
AU - Levy, Mitchell
AU - Lodato, Robert F.
AU - Ismail, Preeti M.
AU - Reese, Amber
AU - Schaumberg, John P.
AU - Malik, Rajesh
AU - Dellinger, R. Phillip
PY - 2013/3
Y1 - 2013/3
N2 - OBJECTIVES: 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. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter phase 2 trial. SETTING: Adult ICUs and emergency departments in the United States. PATIENTS: One hundred ninety-four adults within 24 hrs of the onset of severe sepsis. INTERVENTIONS: Enterally administered talactoferrin 1.5g or placebo every 8 hrs for up to 28 days or until discharge from the ICU. MEASUREMENTS AND MAIN 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.
AB - OBJECTIVES: 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. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter phase 2 trial. SETTING: Adult ICUs and emergency departments in the United States. PATIENTS: One hundred ninety-four adults within 24 hrs of the onset of severe sepsis. INTERVENTIONS: Enterally administered talactoferrin 1.5g or placebo every 8 hrs for up to 28 days or until discharge from the ICU. MEASUREMENTS AND MAIN 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.
KW - Lactoferrin
KW - Septic shock
KW - Severe sepsis
KW - Talactoferrin alfa
UR - http://www.scopus.com/inward/record.url?scp=84874886669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874886669&partnerID=8YFLogxK
U2 - 10.1097/CCM.0b013e3182741551
DO - 10.1097/CCM.0b013e3182741551
M3 - Article
C2 - 23425819
AN - SCOPUS:84874886669
SN - 0090-3493
VL - 41
SP - 706
EP - 716
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 3
ER -