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.
Multicenter, randomized, placebo-controlled, phase II/III clinical study.
Seventy-seven centers in 10 countries.
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.
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.
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.
Administration of oral talactoferrin was not associated with reduced 28-day mortality in patients with severe sepsis and may even be harmful.
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.
Trial registration: ClinicalTrials.gov NCT01273779.
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Dr. Vincent received grant support, consulted for, and received support for travel from Agennix. Dr. Marshall served as a board member for the International Forum for Acute Care Trialists (Chair), World Federation of Societies of Intensive and Critical Care Medicine (Secretary General), International Severe Acute Respiratory and Emerging Infections Consortium (Vice Chair), Asahi Kasei Pharma Data Monitoring Committee member, Spectral Diagnostics (Steering Committee), Center for Sepsis Control and Care Advisory Board, Steering Committee, PROWESS Shock—Eli Lilly, and Roche Diagnostics. His institution received grant support from the Canadian Institutes for Health Research and the Physicians’ Services Incorporated Foundation. Dr. Dellinger received support for travel from Agennix for the Oral tAlactoferrin in Severe sepsIS (OASIS) Advisory Board. His institution received funds for consulting for the EUPHRATES Study, Spectral Dx (also a study looking at intervention [endotoxin removal] in septic shock) and received grant support for his role as Investigator for EUPHRATES Study and Medical Director for the Coordinating Center for that study. Dr. Simonson was employed by Agennix. Dr. Guntupalli served as a board member (steering committee member for the study no payment received for this membership), received support for travel (air ticket—one meeting trip to present data 4 yr ago for an earlier study), received honoraria for presentations related to the study, and was a steering committee member for the OASIS study. Her institution received grant support from the Baylor College of Medicine (for the conduct of the study) and funds from Agennix (study center). Dr. Levy’s institution received grant support from Agennix (site for OASIS trial clinical coordinating center). Dr. Singer was a member of the OASIS Advisory Board and undertook preclinical studies with an educational grant from Agennix, and he consulted for Agennix and received support for travel. His institution received grant support from Agennix. Dr. Malik was employed by and has stock in Agennix.
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