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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by University Hospital, Geneva
Sponsor:
Information provided by (Responsible Party):
Pavlovic Gordana, MD, University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01646229
First received: July 18, 2012
Last updated: August 6, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention
Abdominal Sepsis
Peritonitis
Colon Perforation
Other: Polymyxin-B hemoperfusion
Other: Control

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Impact of Early Per-operative Use of Polymyxin-B Hemoperfusion in Septic Patients Undergoing Emergent Abdominal Surgery

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • The secondary endpoint will be the 90-days mortality [ Time Frame: The 90-days mortality will be assessed on day 90 post PMX hemoperfusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01646229

Contacts
Contact: Gordana Pavlovic, MD +41 795532098 gordana.pavlovic@hcuge.ch

Locations
Switzerland
Emergency operating room, Geneva Cantonal Hospital Recruiting
Geneva, Switzerland, 1211
Contact: Gordana Pavlovic, MD    +41 795532098    gordana.pavlovic@hcuge.ch   
Principal Investigator: Gordana Pavlovic, MD         
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Study Director: Jerome Pugin, Professor Hôpitaux Universitaires de Genève
  More Information

No publications provided

Responsible Party: Pavlovic Gordana, MD, Principal Investigator, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01646229     History of Changes
Other Study ID Numbers: NAC11-054(CC11-146)
Study First Received: July 18, 2012
Last Updated: August 6, 2012
Health Authority: Switzerland: Swiss Medic

Keywords provided by University Hospital, Geneva:
Hemoperfusion
Polymyxin-B
Emergency abdominal surgery
Sepsis
Endotoxin

Additional relevant MeSH terms:
Peritonitis
Sepsis
Peritoneal Diseases
Digestive System Diseases
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Polymyxin B
Polymyxins
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014