Effects of Hemoperfusion With a Polymyxin B Membrane in Peritonitis With Septic Shock (ABDO-MIX)

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock; Peritonitis
• Intervention / Treatment: Device: standard therapy; Device: hemoperfusion

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.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63058
    • Clermont-Ferrand University Hospital
  • Dieppe, France, 76202
    • Dieppe Hospital
  • La Roche sur Yon, France, 85925
    • Vendée Hospital
  • Lens, France, 62307
    • Dr Schaffner Hospital
  • Lille, France, 59037
    • Lille University Hospital
  • Limoges, France, 87042
    • Limoges university hospital
  • Orleans, France, 45067
    • La Source Hospital
  • Paris, France, 75010
    • Lariboisiere University Hospital
  • Paris, France, 75475
    • Saint Louis Hospital
  • Perpignan, France, 66046
    • Saint Jean Hospital
  • Pessac, France, 33600
    • Bordeaux University Hospital
  • Poitiers, France, 86021
    • Poitiers university hospital
  • Rennes, France, 35033
    • Pontchaillou University Hospital
  • Roanne, France, 42300
    • Roanne Hospital
  • Rouen, France, 76031
    • ROUEN university hospital
  • Saint-Malo, France, 35403
    • Saint-Malo Hospital
  • Strasbourg, France, 67091
    • Strasbourg university hospital
  • Tours, France, 37044
    • Tours University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard therapy; 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; 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
Experimental: Hemoperfusion; standard therapy + 2 sessions of hemoperfusion within the first 24 hours	Device: standard therapy; 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: hemoperfusion; 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.; Other Names: toraymyxin; PMX-20R

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality	28 days

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Meditor SAS
• Investigators: Principal Investigator: Didier Payen, MD, Lariboisiere University Hospital; Principal Investigator: René Robert, MD, Poitiers university hospital

Publications and helpful links

General Publications

• Payen DM, Guilhot J, Launey Y, Lukaszewicz AC, Kaaki M, Veber B, Pottecher J, Joannes-Boyau O, Martin-Lefevre L, Jabaudon M, Mimoz O, Coudroy R, Ferrandiere M, Kipnis E, Vela C, Chevallier S, Mallat J, Robert R; ABDOMIX Group. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med. 2015 Jun;41(6):975-84. doi: 10.1007/s00134-015-3751-z. Epub 2015 Apr 11.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: October 8, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Estimate): December 18, 2013
• Last Update Submitted That Met QC Criteria: December 17, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: septic shock; peritonitis; hemoperfusion; endotoxin; Polymyxin B
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Peritoneal Diseases; Sepsis; Intraabdominal Infections; Shock, Septic; Shock; Peritonitis
• Other Study ID Numbers: 2010-67-PMX