The Effects of Polymyxin-B Protects on Sepsis Induced Kidney Dysfunction: a Randomized Clinical Trial

Phase 3

Completed

• Conditions: Gram-Negative Bacterial Infections; Sepsis
• Interventions: Device: Polymyxin -B fiber hemoperfusion system

• Registration Number: NCT00490477
• Lead Sponsor: University of Turin, Italy

Brief Summary

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

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 lipopolysaccharide (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.

Study Timeline

• Study Start: 2006-05
• Status Verified: 2007-06
• Study First Submitted: 2007-06-20
• Study First Submitted QC: 2007-06-21
• Study First Posted: 2007-06-22
• Primary Completion: 2007-07
• Study Completion: 2007-12
• Results First Submitted: 2010-03-09
• Results First Submitted QC: 2010-05-06
• Results First Posted: 2010-06-04
• Last Update Submitted: 2010-06-04
• Last Update Posted: 2010-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Endotoxemia associated to severe sepsis

Exclusion Criteria

• Age < 18 years old
• Organ transplantation
• Hemorrhagic shock
• Thrombophilia
• Chronic renal failure
• Cardiogenic shock
• APACHE II score > 30
• Lack of consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
POLYMYXIN-B	Polymyxin -B fiber hemoperfusion system	an extracorporeal LPS removal

Primary Outcome Measures

Name	Time	Method
Number of Participants Not Requiring Renal Replacement Therapy (RRT)	28 days from the admission

Secondary Outcome Measures

Name	Time	Method
The Reduction of the Number of Apoptotic Cells, Stimulated With Plasma Derives From Septic Patients With Gram Negative Infection, Treated With PMX-B Hemoperfusion, on Immortalized Tubular and Glomerular Cell Cultures.	72 hours after randomization

Trial Locations

Locations (1)

University of Turin, Department of anesthesia and Intensive Care Medicine; 🇮🇹 Turin, Italy