Polymyxin-B Protects From Sepsis Induced Kidney Dysfunction: a Randomized Clinical Trial

Condition(s) targeted: Gram-Negative Bacterial Infections; Sepsis

Intervention: Polymyxin -B fiber hemoperfusion system (Device)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of Turin, Italy

Official(s) and/or principal investigator(s):
marco ranieri, MD, Study Director, Affiliation: University of Turin, Department of Anesthesia and Intensive Care Medicine
marco ranieri, MD, Principal Investigator, Affiliation: University of Turin, Department of Anesthesia and Intensive Care Medicine

Overall contact:
marco ranieri, MD, Phone: 00390116334001, Email: marco.ranieri@unito.it

Aim of the study is to verify whether Polymyxin-B hemoperfusion protects from renal dysfunction in patients with severe sepsis from gram negative infection

Study design: Prevention, Randomized, Open Label, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Verify whether LPS removal with PMX-B hemoperfusion protects from acute renal injury, reducing the need for Renal Replacement Therapy (RRT), in patients with severe sepsis from gram negative infection

Secondary outcome: Verify the reduction of pro-apoptotic activity of plasma derives from septic patients with gram negative infection, treated with PMX-B hemoperfusion, on immortalized tubular and glomerular cell cultures.

Detailed description: Acute renal failure (ARF) is a frequent complication in sepsis, in nearly to 50% of the cases, and the mortality rate is higher, compare to patients with ARF alone (70% vs 45%). Clinical and experimental studies demonstrated the key role of apoptosis, or programmed cell death, in the induction of tubular and glomerular injury in the course of sepsis. Indeed, it has been shown that inflammatory cytokines and LPS cause renal tubular cell apoptosis via Fas- and caspase-mediated pathways. In addition, LPS is able to alter the normal expression pattern of sodium, urea and glucose renal transporters and to modulate tubular polarity by changing the expression of tight junction proteins with consequent back-leakage of tubular fluid in the interstitial spaces and enhancement of the inflammatory process. Therefore a novel extracorporeal therapy to remove circulating LPS, using the Polymyxin-B fiber (PMX-B) cartridge was developed. The PMX-B cartridge is an extracorporeal hemoperfusion device and consists of a polystyrene-based, fibrous adsorbent on which the polymyxin B antibiotic is covalently immobilized as a ligand to adsorb endotoxin.

Aim of this study is to verify whether the removal of LPS, using the PMX-B hemoperfusion system, protects from acute renal failure, reduces the need for Renal Replacement Therapy (RRT) and consequently improves the outcome in severe sepsis from gram negative infection.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Endotoxemia associated to severe sepsis

Exclusion Criteria:

- Age < 18 years old

- Organ transplantation

- Hemorrhagic shock

- Trombofilia

- Chronic renal failure

- Cardiogenic shock

- APACHE II score > 30

- Lack of consent

marco ranieri, MD, Phone: 00390116334001, Email: marco.ranieri@unito.it

University of Turin, Department of anesthesia and Intensive Care Medicine, Turin 10126, Italy; Recruiting
marco ranieri, MD, Phone: 00390116334001, Email: marco.ranieri@unito.it
daniela pasero, MD, Phone: 00390116334002, Email: dpasero@molinette.piemonte.it
daniela pasero, MD, Sub-Investigator
vincenzo cantaluppi, MD, Sub-Investigator
barbara assenzio, Sub-Investigator

Starting date: July 2006
Ending date: December 2007
Last updated: June 21, 2007