Impact of Early Peri-operative Use of Polymyxin-B Hemoperfusion in Septic Patients Undergoing Emergent Abdominal Surgery

April 20, 2019 updated by: Pavlovic Gordana, MD, University Hospital, Geneva

Impact of Early Per-operative Use of Polymyxin-B Hemoperfusion in Septic Patients Undergoing Emergent Abdominal Surgery

Septic shock of intra-abdominal origin is likely due to Gram-negative bacteria or mixed pathogens and associated with high levels of endotoxin. The injury to the endothelium results in an increase of endothelial permeability, interstitial edema and release of nitric oxide (NO) that is a very potent vasodilatator. [6] Polymyxins obtained from the Gram-positive bacterium Bacillus polymyxa are antibiotics known for their ability to bind LPS in the outer membrane of the Gram-negative bacterial cell wall as well as free endotoxins with high affinity. Polymyxin-B has been shown to block the activation of cells by a wide variety of LPS. Studies converged to show an improvement in the treatment of septic shock by removing circulating endotoxin.Starting Polymyxin-B hemoperfusion during the operative time is to block the initiation of various deleterious biological cascades induced by endotoxemia such as systemic inflammation, disseminated coagulation disorders, and shock, leading to organ dysfunction and death.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Geneva, Switzerland, 1211
        • Emergency operating room, Geneva Cantonal Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Adults > 18 years
  • Severe sepsis*or septic shock as define by the ACCCP/SCCM consensus conference, of abdominal origin
  • Need for emergent abdominal surgery procedure under general anesthesia with expected duration of ≥ 120 min (in and out patients) for bowel perforation, ileus or peritonitis

Exclusion Criteria:

  • Patients younger than 18 years
  • Organ transplantation in the last year
  • Terminally ill patients: do-not-resuscitate order, perceived to die within 48 hrs of admission
  • Known pregnancy or diagnosed by US or Ct-scan (>14 weeks)
  • History of sensitivity to polymyxin-B or to anticoagulant ( heparin)
  • Uncontrolled hemorrhage within the last 24h
  • Severe granulocytopenia ( leukocyte count of < 500/µL)
  • Severe thrombocytopenia ( platelets count of < 30'000/µL)
  • Need for CPR pre-operatively

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Polymyxin-B hemoperfusion
In the HEMOPERFUSION group, a veno-venous dialysis catheter type GamCath 12 F, 3 lumen will be inserted instead of a regular double or triple-lumen central venous catheter, and connected to the Toraymyxin® (PMX-20-R) device for endotoxin adsorption by hemoperfusion with the DECAPSMART pump. The length of the hemoperfusion will be a minimum of 120 min and started just before the beginning of the surgical intervention in the OR and stopped at the end of surgery.
Other: Polymyxin-B hemoperfusion
Active Comparator: Control

In the CONTROL group, the administration of fluids (250 to 500ml crystalloids) and cardiovascular supportive drugs will be guided to maintain standard pressure-related parameters within a normal range: MAP > 65mmHg, HR < 90/min, CVP between > 8 and 12 < mmHg, urinary output > 0.5 ml/kg/h. In line with the conventional approach, other physiological parameters will also be targeted: T° > 35.5°C, Sp02 > 95%, lactate < 2.5 mMol/L, normalisation of the BE.

At the discretion of the attending anaesthesiologist with the FMH level, a PiCCO monitoring, a transoesophageal echography, or a pulmonary artery catheter, will be inserted to complement the standard hemodynamic monitoring if deemed necessary.
Other: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoint will be requirement of vasopressors during the first 72 hrs after the beginning of the PMX hemoperfusion using the "inotropic score"
Time Frame: The inotropic score is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
The inotropic score is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.

Secondary Outcome Measures

Outcome Measure
Time Frame
The secondary endpoint will be the variation of MAP, during the first 72 hrs after the beginning of the PMX hemoperfusion
Time Frame: The inotropic score is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
The inotropic score is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
The secondary endpoint will be the variation of "vasopressor dependency index", during the first 72 hrs after the beginning of the PMX hemoperfusion
Time Frame: The variation of the "vasopressor dependency index" is assessed at: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
The variation of the "vasopressor dependency index" is assessed at: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
The secondary endpoint will be the variation of Pa02/Fi02, during the first 72 hrs after the beginning of the PMX hemoperfusion
Time Frame: The variation of Pa02/Fi02 is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
The variation of Pa02/Fi02 is assessed at the following specific time points: Time 0 - baseline measurements at the beginning of surgery, second time point at the end of surgery, Time 0 +6 hours, Time 0 + 24 hours, Time 0 + 48 hours, Time 0 + 72 hours.
The secondary endpoint will be the variations of the total SOFA score during the first 7 days after the beginning of the PMX hemoperfusion
Time Frame: The variations of the total SOFA score will be assessed once a day from day 1, till discharge of the ICU, and this maximaly 7 days after the beginning of the PMX hemoperfusion
The variations of the total SOFA score will be assessed once a day from day 1, till discharge of the ICU, and this maximaly 7 days after the beginning of the PMX hemoperfusion
The secondary endpoint will be the 28-days mortality
Time Frame: The 28-days mortality will be assessed on the 28th day post PMX hemoperfusion
The 28-days mortality will be assessed on the 28th day post PMX hemoperfusion
The secondary endpoint will be the 90-days mortality
Time Frame: The 90-days mortality will be assessed on day 90 post PMX hemoperfusion
The 90-days mortality will be assessed on day 90 post PMX hemoperfusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Geneva

Investigators

  • Study Director: Jerome Pugin, Professor, Hôpitaux Universitaires de Genève

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

July 18, 2012

First Submitted That Met QC Criteria

July 18, 2012

First Posted (Estimate)

July 20, 2012

Study Record Updates

Last Update Posted (Actual)

April 23, 2019

Last Update Submitted That Met QC Criteria

April 20, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NAC11-054(CC11-146)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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