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

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ClinicalTrials.gov Identifier: NCT01646229
Recruitment Status : Completed
First Posted : July 20, 2012
Last Update Posted : May 13, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment
Abdominal Sepsis Peritonitis Colon Perforation Other: Polymyxin-B hemoperfusion Other: Control

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Impact of Early Per-operative Use of Polymyxin-B Hemoperfusion in Septic Patients Undergoing Emergent Abdominal Surgery
Study Start Date : January 2012
Primary Completion Date : December 2014
Study Completion Date : February 2015

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U.S. FDA Resources

Arms and Interventions

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


Outcome Measures

Primary Outcome Measures :
  1. 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. ]

Secondary Outcome Measures :
  1. 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. ]
  2. 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. ]
  3. 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. ]
  4. 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 ]
  5. 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 ]
  6. The secondary endpoint will be the 90-days mortality [ Time Frame: The 90-days mortality will be assessed on day 90 post PMX hemoperfusion ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01646229


Locations
Switzerland
Emergency operating room, Geneva Cantonal Hospital
Geneva, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Study Director: Jerome Pugin, Professor Hôpitaux Universitaires de Genève
More Information

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)
First Posted: July 20, 2012    Key Record Dates
Last Update Posted: May 13, 2016
Last Verified: May 2016

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

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