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

This study has been completed.
Sponsor:
Information provided by:
University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT00490477
First received: June 20, 2007
Last updated: June 4, 2010
Last verified: June 2007
  Purpose

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


Condition Intervention Phase
Gram-Negative Bacterial Infections
Sepsis
Device: Polymyxin -B fiber hemoperfusion system
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Polymyxin-B Hemoperfusion Inactivates Circulating Proapoptotic Factors

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

Primary Outcome Measures:
  • Number of Participants Not Requiring Renal Replacement Therapy (RRT) [ Time Frame: 28 days from the admission ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 72 hours after randomization ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: May 2006
Study Completion Date: December 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: CONVENTIONAL
Active Comparator: POLYMYXIN-B
an extracorporeal LPS removal
Device: Polymyxin -B fiber hemoperfusion system
two hours treatment for two days
Other Name: PMX-B

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00490477

Locations
Italy
University of Turin, Department of anesthesia and Intensive Care Medicine
Turin, Italy, 10126
Sponsors and Collaborators
University of Turin, Italy
Investigators
Study Director: marco ranieri, MD University of Turin, Department of Anesthesia and Intensive Care Medicine
Principal Investigator: marco ranieri, MD University of Turin, Department of Anesthesia and Intensive Care Medicine
  More Information

Publications:
Responsible Party: V. M. Ranieri, MD, University of Turin
ClinicalTrials.gov Identifier: NCT00490477     History of Changes
Other Study ID Numbers: N-257
Study First Received: June 20, 2007
Results First Received: March 9, 2010
Last Updated: June 4, 2010
Health Authority: Italy: Ministry of Health

Keywords provided by University of Turin, Italy:
acute renal failure
lipopolysaccharide
tubular apoptosis
Polymyxin-B fiber
Severe sepsis from gram negative infection

Additional relevant MeSH terms:
Infection
Sepsis
Toxemia
Bacterial Infections
Gram-Negative Bacterial Infections
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Polymyxin B
Polymyxins
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014