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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by University Hospital, Geneva.
Recruitment status was  Recruiting
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

July 18, 2012
August 6, 2012
January 2012
December 2013   (final data collection date for primary outcome measure)
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 ]
The primary endpoint will be requirement of vasopressors during the 72 hrs after the beginning of the PMX hemoperfusion using the "inotropic score" [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01646229 on ClinicalTrials.gov Archive Site
  • 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 ]
Variation of MAP, Pa02/Fi02,the total SOFA score and 28- and 90-day mortality. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary endpoints:

  • Variation of the "vasopressor dependency index"
  • Variation of MAP,
  • Variations of the Pa02/Fi02,
  • Variations of the total SOFA score
  • 28- and 90-day mortality In addition, other secondary endpoints will be assessed, such as the quantity of fluid requirement and fluid balance, the time of mechanical ventilation, the evolution of renal function, the evolution of arterial lactate levels, and the length of stay in the ICU and in the hospital.
Not Provided
Not Provided
 
Impact of Early Peri-operative Use of Polymyxin-B Hemoperfusion in Septic Patients Undergoing Emergent Abdominal Surgery
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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Abdominal Sepsis
  • Peritonitis
  • Colon Perforation
  • Other: Polymyxin-B hemoperfusion
  • Other: Control
  • 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.
    Intervention: 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.

    Intervention: Other: Control
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
December 2013
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Gordana Pavlovic, MD +41 795532098 gordana.pavlovic@hcuge.ch
Switzerland
 
NCT01646229
NAC11-054(CC11-146)
Yes
Pavlovic Gordana, MD, University Hospital, Geneva
University Hospital, Geneva
Not Provided
Study Director: Jerome Pugin, Professor Hôpitaux Universitaires de Genève
University Hospital, Geneva
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP