Gram-Negative Bacterial Infections, Sepsis
Conditions
Keywords
acute renal failure, lipopolysaccharide, tubular apoptosis, Polymyxin-B fiber, Severe sepsis from gram negative infection
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.
Interventions
DEVICEPolymyxin -B fiber hemoperfusion system
two hours treatment for two days
Sponsors
University of Turin, Italy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Not Requiring Renal Replacement Therapy (RRT) | 28 days from the admission |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Conventional Treatment (CONV) patients with Gram-negative severe sepsis who received standard care according to Surviving Sepsis Campaign guidelines | 8 |
| Polymyxin-B Hemoperfusion Treatment (PMX-B) patients with Gram-negative severe sepsis treated with standard therapy, according to the Surviving Sepsis Campaign, and an extracorporeal therapy with a PMX-B filter that could remove LPS | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Polymyxin-B Hemoperfusion Treatment (PMX-B) | Conventional Treatment (CONV) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 10 Participants |
| Age Continuous | 61 years STANDARD_DEVIATION 10 | 59 years STANDARD_DEVIATION 13 | 60 years STANDARD_DEVIATION 11 |
| Region of Enrollment Italy | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants Not Requiring Renal Replacement Therapy (RRT)
Time frame: 28 days from the admission
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conventional Treatment (CONV) | Number of Participants Not Requiring Renal Replacement Therapy (RRT) | 3 participants |
| Polymyxin-B Hemoperfusion Treatment (PMX-B) | Number of Participants Not Requiring Renal Replacement Therapy (RRT) | 1 participants |
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.
Time frame: 72 hours after randomization