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Crit Care Med. 2015 Sep;43(9):1832-8. doi: 10.1097/CCM.0000000000001090.

Talactoferrin in Severe Sepsis: Results From the Phase II/III Oral tAlactoferrin in Severe sepsIS Trial.

Author information

1
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.

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.

DESIGN:

Multicenter, randomized, placebo-controlled, phase II/III clinical study.

SETTING:

Seventy-seven centers in 10 countries.

PATIENTS:

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.

INTERVENTIONS:

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.

MEASUREMENTS AND MAIN 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01273779.

Comment in

PMID:
26010687
DOI:
10.1097/CCM.0000000000001090
[Indexed for MEDLINE]

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