Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis (EUPHAS)

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

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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Gram-Negative Bacterial Infections; Septic Shock
• Intervention / Treatment: Device: Polymyxin B immobilized fiber column; Other: Conventional medical therapy in the ICU

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Vicenza, Italy, 36100
    • St Bortolo 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:

• 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

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
Experimental: 1	Device: Polymyxin B immobilized fiber column; 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.; Other Names: Toraymyxin; Other: Conventional medical therapy in the ICU; 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.
Other: 2	Other: Conventional medical therapy in the ICU; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: St. Bortolo Hospital

Publications and helpful links

General Publications

• Cruz DN, Perazella MA, Bellomo R, de Cal M, Polanco N, Corradi V, Lentini P, Nalesso F, Ueno T, Ranieri VM, Ronco C. Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review. Crit Care. 2007;11(2):R47. doi: 10.1186/cc5780.
• Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, Malcangi V, Petrini F, Volta G, Bobbio Pallavicini FM, Rottoli F, Giunta F, Ronco C. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009 Jun 17;301(23):2445-52. doi: 10.1001/jama.2009.856.

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: February 26, 2008
• First Submitted That Met QC Criteria: March 5, 2008
• First Posted (Estimate): March 6, 2008

Study Record Updates

• Last Update Posted (Estimate): December 2, 2008
• Last Update Submitted That Met QC Criteria: December 1, 2008
• Last Verified: April 1, 2008

More Information

Terms related to this study

• Keywords: septic shock; abdominal surgery; hemoperfusion; abdominal sepsis; polymyxin B; Endotoxins
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Shock, Septic; Shock; Bacterial Infections; Gram-Negative Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Polymyxins; Polymyxin B
• Other Study ID Numbers: TM05