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

Sepsis Clinical Trial

Official title:

Polymyxin-B Hemoperfusion Inactivates Circulating Proapoptotic Factors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00490477
• Other study ID #: N-257
• Status: Completed
• Phase: Phase 3
• First received: June 20, 2007
• Last updated: June 4, 2010
• Start date: May 2006
• Est. completion date: December 2007

Study information

• Verified date: June 2007
• Source: University of Turin, Italy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bacterial Infections
• Gram-Negative Bacterial Infections
• Sepsis

Intervention

Device:
• Polymyxin -B fiber hemoperfusion system
two hours treatment for two days

Locations

Country	Name	City	State
Italy	University of Turin, Department of anesthesia and Intensive Care Medicine	Turin

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Cantaluppi V, Assenzio B, Pasero D, Romanazzi GM, Pacitti A, Lanfranco G, Puntorieri V, Martin EL, Mascia L, Monti G, Casella G, Segoloni GP, Camussi G, Ranieri VM. Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors. Intensive Care Med — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Not Requiring Renal Replacement Therapy (RRT)		28 days from the admission	No
Secondary	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	No