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

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:

MedlinePlus related topics: Bacterial Infections Dietary Fiber Sepsis

Drug Information available for: Polymyxin B Polymyxin B sulfate

U.S. FDA Resources

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

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:

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. 2008 Sep;34(9):1638-45. Epub 2008 May 8.

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:

Bacterial Infections
Sepsis
Toxemia
Gram-Negative Bacterial Infections
Infection
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 May 16, 2013