Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis

Study Overview
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Brief Summary
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This clinical study designed as a prospective, open labelled, multi-centre, RCT will be carried out to evaluate if direct hemoperfusion with polymyxin B immobilized fiber column (PMX) is superior to conventional medical therapy for sepsis, for patients with sepsis arising from abdominal cavity infection, accompanied by the failure of one or more organs. 120 patients (60 treatment/60 control) will be considered in this study. Those patients fulfilling inclusion criteria and not having exclusion criteria will be randomly allocated to one of two study groups. One group will be treated with PMX (PMX group) and the other will receive a standard therapy for sepsis (control group). All patients will receive full intensive care management, including fluid resuscitation, vasopressors, antimicrobial chemotherapy, ventilatory support, and renal replacement therapy, if required. Each patient will be followed up for 28 days after study entry.

Official Title
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Dispositivo Adsorbente Con Polymyxina B Immobilizzata Nello Shock Settico - Studio Clinico Randomizzato e Prospettico, Multicentrico

Conditions
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Gram-Negative Bacterial Infections, Sepsis, Septic Shock

Intervention / Treatment
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* Device: Polymyxin B immobilized fiber column
* Other: Conventional medical therapy in the ICU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe sepsis due to intra-abdominal cavity infection after emergency surgery with at least 2 SIRS criteria and 1 organ dysfunction (as defined by SCCM) Exclusion Criteria: Less than 18 years of age Females with a positive pregnancy test Treated with another investigational drug or device within the 30 days immediately preceding enrolment in this study Undergone organ transplantation during the past one year Documented history of sensitivity to Polymyxin-B, anticoagulant (heparin) Terminally ill, including metastases or hematological malignancy, with a life expectancy less than 30 days (as assessed by the attending physician) or have been classified as Do Not Resuscitate Diagnosed with HIV Previous history of end stage chronic organ failure(s) Uncontrolled hemorrhage within the last 24 h Diagnosed with granulocytopenia (leukocyte count of less than 500 cells/mm3) and/or thrombocytopenia (platelet count of less than 30,000 cells/mm3) More than 4 failed organs at entry An APACHE II score of more than 30 at entry to the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Device: Polymyxin B immobilized fiber column<br>* Hemoperfusion with PMX will be performed in ICU. The 1st PMX treatment (day 0) will be carried out for 2 hours and ideally within 24 hours but not later than 48 hours after diagnosis of severe sepsis. The second PMX treatment has to be performed 24 to 48 hours after the end of the first PMX treatment, ideally after 24 hours. Hemoperfusion therapy will be performed in addition to conventional medical therapy in the ICU.<br>* Other names: Toraymyxin;Other: Conventional medical therapy in the ICU<br>* Including, but not limited to: antibiotic therapy, nutrition, administration of gamma-globulins, vasopressors, hemodynamic monitoring, organ support in the ICU including mechanical ventilation, corrective measures for metabolic abnormalities, renal replacement therapy when appropriate.<br>|
| Other: 2<br> | Other: Conventional medical therapy in the ICU<br>* Including, but not limited to: antibiotic therapy, nutrition, administration of gamma-globulins, vasopressors, hemodynamic monitoring, organ support in the ICU including mechanical ventilation, corrective measures for metabolic abnormalities, renal replacement therapy when appropriate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure and use of vasopressors |  | 48-72 hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PaO2/ FiO2 ratio |  | 48-72 hrs | 
| Change in SOFA score |  | 48-72 hrs | 
| ICU survival |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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abdominal sepsis, abdominal surgery, septic shock, polymyxin B, hemoperfusion, Endotoxins