Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial.
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Serval ID
serval:BIB_D9D85D301E8D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial.
Journal
Critical Care Medicine
Working group(s)
Patient Outcomes in Sepsis (LIPOS) Investigators
Contributor(s)
Lipid Infusion, Blejman S., Cahn P., Conforti A., Farina O., San Juan J., Maskin B., Nul D., Romero E., Bellomo R., Finfer S., French C., Van Heerden P., Joannidis M., Spiss CK., Demeyer I., Dugernier T., De Jongh R., Laterre PF., Oeyen S., Spapen H., Vincent JL., Wilmer A., Antoniazzi P., Cunha£££Clóvis£££ C. , Silva E., Albert M., Aslanian P., Bishop G., Dos Santos C., Dubois MJ., Fenwick J., Goldberg P., Grimard D., Hall R., Herridge M., Hooper J., Keenan S., Kumar A., Kutsogiannis D., Laupland K., McIntyre L., Piche A., Poirier G., Russell JA., Tremblay L., Trottier S., Wong A., Wood G., Skrobik Y., Barreto ML., Inzunza RA., Norambuena MM., Kasal E., Svoboda P., Kivistik U., Sarapuu S., Fedossov V., Ala-Kokko T., Hovilehto S., Hynninen M., Karlsson S., Laine H., Laru-Sompa R., Parviainen I., Ruokonen E., Saarinen K., Tenhunen J., Bedos JP., Capdevila X., Dhainaut JF., François B., Gissot V., Holzappel L., Lefrant JY., Martin C., Offenstadt G., Boldt J., Brodt HR., Forycki F., Frei U., Fritz HG., Gründling M., Kalenk A., Klett I., Kljucar S., Klöss T., Kujath P., Larsen R., Machill K., Meier-Hellmann A., Mertzlufft F., Motsch J., Motsch J., Müller T., Nöldge-Schomburg G., Olthoff D., Peckelsen C., Piepenbrock S., Putensen C., Quintel M., Ragaller M., Reinhart K., Rosolski T., Scholz J., Soukup J., Walger P., Zirngibl H., Baltopoulos G., Bassaris H., Giamarellos-Bourboulis E., Kapravelos N., Karabinis A., Anandaciva S., Cheng G., Law WL., Yip WC., Adhikari P., Kalambe B., Kothari V., Pai V., Ramesh M., Sathe P., Chowers M., Potasman I., Raz R., Choi SH., Kim WJ., Song JH., Kamarulzaman A., Rahman MN., Bakker J., Gerritsen RT., Polderman KH., Roozendaal FW., Spronk PE., Zanten vA., Graham N., Henderson S., McArthur C., Williams A., Catorze N., Miranda I., Costandache FM., Beloborodova N., Gelfand B., Kon E., Kozlov S., Martynenko T., Nikiforov Y., Ogorodova L., Vladimir V., Shlyapnikov S., Vlasova N., Zubareva N., Kremzar B., Muzlovic I., Papuga V., Remec T., Richards G., Raine R., Esteban A., Manuel£££Jiménez Lendínez£££ JL. , Castro MT., Gil£££Cristóbal León£££ CL. , Caballero JM., Ruano M., Mascaró BS., Torrabadella P., Freiberg H., Gårdlund B., Hagberg L., Liu YC., Tsai YH., Wang JH., Yang PC., Permpikul C., Pothirat C., Sittipunt C., Davidson A., Garrioch M., Garrard C., Kapila A., Mallick A., Morrison L., Nolan J., Webster N., Wenstone R., Siever J., Waldon BG., Belzberg H., Cheng E., Pearle J., Turner J., Wong G., Speer JF., Parry M., Bush L., Durham R., Guzzi L., Horiuchi T., Locay H., Vicari R., Demarini T., Eaton S., Friedman B., Kelly M., Vierra J., Margolis B., Tillis W., Fletcher E., Fraiz J., Gervich D., Hata S., Simpson S., Rogers S., Steingrub J., Digiovine B., Saulters R., Pullman J., Dellinger PR., Lucasti C., Tobin E., Dicipinigaitis P., Karwa M., El Solh A., Barie P., Manasia A., Pastores S., Cook P., Intal H., Link A., Heiselman D., Imm A., Chen M., Harless K., Boylan A., Sy A., Swilley J., Weinstein G., Ziegler D., Markewitz B., Baker AM., Quaranta A., LeDoux E., Tural A.
ISSN
1530-0293 (Electronic)
ISSN-L
0090-3493
Publication state
Published
Issued date
2009
Volume
37
Number
11
Pages
2929-2938
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
OBJECTIVE: To assess the survival benefit and safety profile of low-dose (850 mg/kg) and high-dose (1350 mg/kg) phospholipid emulsion vs. placebo administered as a continuous 3-day infusion in patients with confirmed or suspected Gram-negative severe sepsis. Preclinical and ex vivo studies show that lipoproteins bind and neutralize endotoxin, and experimental animal studies demonstrate protection from septic death when lipoproteins are administered. Endotoxin neutralization correlates with the amount of phospholipid in the lipoprotein particles.
DESIGN: A three-arm, randomized, blinded, placebo-controlled trial.
SETTING: Conducted at 235 centers worldwide between September 2004 and April 2006.
PATIENTS: A total of 1379 patients participated in the study, 598 patients received low-dose phospholipid emulsion, and 599 patients received placebo. The high-dose phospholipid emulsion arm was stopped, on the recommendation of the Independent Data Monitoring Committee, due to an increase in life-threatening serious adverse events at the fourth interim analysis and included 182 patients.
MEASUREMENTS AND MAIN RESULTS: A 28-day all-cause mortality and new-onset organ failure. There was no significant treatment benefit for low- or high-dose phospholipid emulsion vs. placebo for 28-day all-cause mortality, with rates of 25.8% (p = .329), 31.3% (p = .879), and 26.9%, respectively. The rate of new-onset organ failure was not statistically different among groups at 26.3%, 31.3%, 20.4% with low- and high-dose phospholipid emulsion, and placebo, respectively (one-sided p = .992, low vs. placebo; p = .999, high vs. placebo). Of the subjects treated, 45% had microbiologically confirmed Gram-negative infections. Maximal changes in mean hemoglobin levels were reached on day 10 (-1.04 g/dL) and day 5 (-1.36 g/dL) with low- and high-dose phospholipid emulsion, respectively, and on day 14 (-0.82 g/dL) with placebo.
CONCLUSIONS: Treatment with phospholipid emulsion did not reduce 28-day all-cause mortality, or reduce the onset of new organ failure in patients with suspected or confirmed Gram-negative severe sepsis.
DESIGN: A three-arm, randomized, blinded, placebo-controlled trial.
SETTING: Conducted at 235 centers worldwide between September 2004 and April 2006.
PATIENTS: A total of 1379 patients participated in the study, 598 patients received low-dose phospholipid emulsion, and 599 patients received placebo. The high-dose phospholipid emulsion arm was stopped, on the recommendation of the Independent Data Monitoring Committee, due to an increase in life-threatening serious adverse events at the fourth interim analysis and included 182 patients.
MEASUREMENTS AND MAIN RESULTS: A 28-day all-cause mortality and new-onset organ failure. There was no significant treatment benefit for low- or high-dose phospholipid emulsion vs. placebo for 28-day all-cause mortality, with rates of 25.8% (p = .329), 31.3% (p = .879), and 26.9%, respectively. The rate of new-onset organ failure was not statistically different among groups at 26.3%, 31.3%, 20.4% with low- and high-dose phospholipid emulsion, and placebo, respectively (one-sided p = .992, low vs. placebo; p = .999, high vs. placebo). Of the subjects treated, 45% had microbiologically confirmed Gram-negative infections. Maximal changes in mean hemoglobin levels were reached on day 10 (-1.04 g/dL) and day 5 (-1.36 g/dL) with low- and high-dose phospholipid emulsion, respectively, and on day 14 (-0.82 g/dL) with placebo.
CONCLUSIONS: Treatment with phospholipid emulsion did not reduce 28-day all-cause mortality, or reduce the onset of new organ failure in patients with suspected or confirmed Gram-negative severe sepsis.
Keywords
Acidosis/epidemiology, Bilirubin/blood, Cholesterol/blood, Cognition Disorders/epidemiology, Dose-Response Relationship, Drug, Double-Blind Method, Fat Emulsions, Intravenous/administration & dosage, Fat Emulsions, Intravenous/adverse effects, Female, Gram-Negative Bacterial Infections/drug therapy, Gram-Negative Bacterial Infections/mortality, Heart Arrest/epidemiology, Hemoglobins/analysis, Humans, Liver Failure/epidemiology, Male, Middle Aged, Multiple Organ Failure/epidemiology, Phospholipids/administration & dosage, Phospholipids/adverse effects, Sepsis/drug therapy, Sepsis/microbiology, Severity of Illness Index
Pubmed
Web of science
Create date
24/11/2009 17:48
Last modification date
20/08/2019 16:59
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