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

NCT01646229 | Completed DMC

• 1 other identifier: NAC11-054(CC11-146)
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Abdominal Sepsis; Peritonitis; Colon Perforation

Keywords

Hemoperfusion; Polymyxin-B; Emergency abdominal surgery; Sepsis; Endotoxin

Outcome Measures

Primary Outcomes (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"

  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 Outcomes (6)

• The secondary endpoint will be the variation of MAP, during the first 72 hrs after the beginning of the PMX hemoperfusion

  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

  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

  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

  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

  The 28-days mortality will be assessed on the 28th day post PMX hemoperfusion

Study Arms (2)

Polymyxin-B hemoperfusion

ACTIVE COMPARATOR

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

Control

ACTIVE COMPARATOR

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

Interventions

Polymyxin-B hemoperfusion OTHER

Polymyxin-B hemoperfusion

Control OTHER

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

Emergency operating room, Geneva Cantonal Hospital

Geneva, 1211, Switzerland

Location

MeSH Terms

Conditions

Intraabdominal Infections; Peritonitis; Sepsis

Condition Hierarchy (Ancestors)

Infections; Peritoneal Diseases; Digestive System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jerome Pugin, Professor

  University Hospital, Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 20, 2012
• Study Start: January 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: February 1, 2015
• Last Updated: April 23, 2019

Record last verified: 2019-04

Locations

CH (1)