Effects of Hemoperfusion With a Polymyxin B Membrane in Peritonitis With Septic Shock

Study Overview
=================
Brief Summary
-----------------
The purpose of this randomized, comparative, open and multi-centre study is to show that two sessions of hemoperfusion with Toraymyxin performed within maximum 36 hours after the surgery of a peritonitis by hollow organ perforation reduce the mortality in patients suffering from septic shock.

Detailed Description
-----------------
The mortality rate due to peritonitis associated to a severe sepsis or a septic shock remains high (between 40 and 60% as per the studies). The recent complementary therapies for severe sepsis have been reassessed (strict glycaemic control, substitutive corticotherapy, activated protein C). Early neutralisation of the endotoxaemia related to gram-negative bacilli sepsis in contact with hemoperfusion membrane covered with polymyxin B (Toraymyxin™) may enable reduction of the inflammatory reaction caused by sepsis and improve its prognosis. 30 studies, including 10 randomized studies, have compared hemoperfusion with Toraymyxin™ to the standard treatment, showing an improvement in the patients' haemodynamic state, oxygenation conditions and reduction in mortality. This treatment is commonly used in Japan. However, the studies conducted either include only a limited number of patients or are not randomized prospective studies. The post-hoc analysis of a recent randomized study conducted on a limited number of patients with abdominal septic shock shows a significant reduction in mortality after factor adjustment. Though the side effects of such a treatment are limited, its cost is high. Hence, extensive prospective studies are necessary to confirm its effectiveness.

Official Title
-----------------
Effects of Hemoperfusion With a Polymyxin B Membrane in Peritonitis With Septic Shock

Conditions
-----------------
Peritonitis, Septic Shock

Intervention / Treatment
-----------------
* Device: standard therapy
* Device: hemoperfusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed community or nosocomial acquired peritonitis due to organ perforation Septic shock requiring catecholamine infusion started or maintained 2 hours after surgery Exclusion Criteria: Pregnancy No severity criteria within the 8 hours following surgery Neutropenia due to chemotherapy or malignancy Abdominal sepsis without peritonitis Mesenteric ischemia without perforation Peritonitis due to appendicitis Perforation linked to trauma Cirrhosis child C Impossibility to use heparin Prolonged cardiac arrest within 72h before surgery Terminal disease diagnosed during surgery Moribund subjects

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard therapy<br>Standard therapy in the ICU including but not limited to: antibiotic therapy, nutrition, fluid challenge, vasopressors, hemodynamic monitoring, organ support in the ICU including mechanical ventilation, renal replacement therapy when appropriate | Device: standard therapy<br>* Standard therapy in the ICU including but not limited to: antibiotic therapy, nutrition, fluid challenge, vasopressors, hemodynamic monitoring, organ support in the ICU including mechanical ventilation, renal replacement therapy when appropriate<br>|
| Experimental: Hemoperfusion<br>standard therapy + 2 sessions of hemoperfusion within the first 24 hours | Device: standard therapy<br>* Standard therapy in the ICU including but not limited to: antibiotic therapy, nutrition, fluid challenge, vasopressors, hemodynamic monitoring, organ support in the ICU including mechanical ventilation, renal replacement therapy when appropriate<br>Device: hemoperfusion<br>* Extracorporeal hemoperfusion with Toraymyxin PMX-20R and conventional medical therapy in the ICU including but not limited to: antibiotic therapy, nutrition, fluid challenge, vasopressors, hemodynamic monitoring, organ support in the ICU including mechanical ventilation, renal replacement therapy when appropriate.<br>* Other names: PMX-20R;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| organ failure assessed by SOFA score |  | day 3 | 
| delay to withdraw catecholamine after initial shock |  | day 1-day 28 | 
| mortality between the two groups at 7 dayx, 14 days, 21 days and 90 days |  | 90 days | 
| number of participants with adverse events related to hemoperfusion technique including anticoagulation therapy such as bleeding (type and number of blood transfusion) |  | day1-day4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
peritonitis, septic shock, hemoperfusion, Polymyxin B, endotoxin