Endotoxin Adsorber Hemoperfusion and Microcirculation

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Taiwan University Hospital
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01756755
First received: December 20, 2012
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

Despite maintaining adequate mean arterial pressure and central venous oxygen saturation, the mortality is still high in severe sepsis and septic shock. Previous studies have demonstrated that derangements in microvascular flow play a role in sepsis-induced multiple organ dysfunction and death. Lipopolysaccharide (LPS) or endotoxin is a specific ligand for Toll-like receptor 4 (TLR4), it can induce the following reactions including excessive immune and inflammatory responses , oxidative stress , capillary leakage, endothelial damage, impaired arteriolar and venular vasoregulation, and activation of the coagulation cascade 8. Subsequently, these reactions can lead to microcirculatory dysfunction. Polymyxin B adsorber hemoperfusion (PMX) have been proved to reduce mortality of severe sepsis and septic shock. Since 1994 to 2007, more than 60,000 patients have received this treatment. In a systematic review, the results show that PMX therapy was associated with significantly lower mortality risk (risk ratio, 0.53; 95% CI, 0.43 to 0.65). In a prospective, multicenter, randomized controlled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]), the results show that SOFA scores improved in the polymyxin B group, and 28-day mortality was 32% in the polymyxin B group and 53% in the conventional therapy group.

The investigators hypothesize that polymyxin B hemoperfusion can decrease blood endotoxin level and reduce endotoxin-related microcirculatory dysfunction. The purpose of this prospective, multicenter, randomized, controlled, open study is to investigate the effect of polymyxin B hemoperfusion on the sublingual microcirculation in patient with proven or suspected gram-negative bacteria severe sepsis and septic shock. The mean arterial pressure, dose of vasopressors and inotropics, SOFA score, PaO2/FiO2 ratio, and 28-day mortality will be investigated.


Condition Intervention Phase
Sepsis
Device: PMX-20R Hemoperfusion
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Endotoxin Adsorber Hemoperfusion on the Microcirculation in Patients With Severe Sepsis and Septic Shock

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Total small vessel density of sublingual microcirculation [ Time Frame: 48h ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change of SOFA score [ Time Frame: 48h ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Number of participates die within 28 days [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2012
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Control
Treat with severe sepsis / septic shock practice guideline
Experimental: PMX HP
Treat with severe sepsis / septic shock practice guideline Treat with PMX-20R Hemoperfusion [Polymyxin B adsorbs and remove endotoxin from the patient's circulating blood].
Device: PMX-20R Hemoperfusion
Polymyxin B adsorbs and remove endotoxin from the patient's circulating blood.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients will be included in this study if they meet the following criteria (A+B+C):

A. Patients with the following conditions:

  1. Abdominal cavity infection following emergency surgery.
  2. Pneumonia, blood stream infection, urinary tract infection, or other infection, has received adequate treatment and presents with an Endotoxin Activity Assay > 0.6 EAA units.

B. SIRS, as defined by the presence of at least 2 of the following conditions (These criteria should have occurred between 12 hours before or 6 hours after the onset of the qualifying first organ dysfunction :

  1. Fever or hypothermia (body temperature over 38 ℃ or under 36 ℃)
  2. Tachycardia (heart rate > 90 bpm)
  3. Tachypnea (respiratory rate over 20 breaths/min or under mechanical ventilation)
  4. Leukocyte count more than 12,000 cells/mm3, less than 4,000 cells/mm3, or more than 10 % of immature form (band)

C. The presence of at least one of these symptoms of organ dysfunction or shock:

  1. Cardiovascular system: an SBP of less than 90 mm Hg, a decrease in SBP of at least 40 mm Hg from baseline, a MAP of less than 65 mm Hg, or that requires treatments with vasoactive medication at any dosage.
  2. Acute lung injury: PaO2 / FiO2 ratio less than 300 (ratio in mm Hg)
  3. Acute kidney injury: creatinine more than 2 mg/dL, an increase in creatinine of more than 0.5 mg/dL, or diuresis of less than 0.5 mL/kg/h for 2 hours.
  4. Acute liver injury: Total bilirubin level more than 4 mg/dL
  5. Disseminated intravascular coagulation: platelet count less than 100,000 cells/mm3 or a reduction of more than 50 % of baseline
  6. INR > 1.5 or aPTT > 60 sec
  7. Altered mental status: GCS under 13 or 9T under endotracheal tube
  8. Lactic acidosis: Lactate level more than 2 mmol/L (accompany with pH < 7.3 or Base excess < -5 mmol/L)

Exclusion Criteria:

Patients will be excluded if they

A. are under 20 years old or older than 99 years old

B. have suffered from severe sepsis or septic shock more than 24 hours

C. are pregnant

D. were treated with another medicine or device in the trial less than 30 days prior to the admission to this trial

E. have received organ transplantation less than 1 years prior to this trial

F. patients with hemophilia

G. have a allergic history of polymyxin B, heparin, or extracorporeal circulation

H. are terminally ill, for examples with metastasis, with a life expectancy of less than 30 days (certified by the attending physician)

I. have been diagnosed with HIV

J. present uncontrolled bleeding in the last 24 hours

K. were diagnosed with leukocytopenia (leukocyte count less than 500 cell/mm3) and/or thrombocytopenia (platelet count less than 50,000 cells/mm3)

L. have already received other blood cleaning treatments, such as CVVH, HD, HF, and PE upon entry into the trial

M. have a prior history of severe chronic organ failure

  1. chronic respiratory failure ( COPD at last stage)
  2. chronic heart failure (NYHA score = IV)
  3. brain death
  4. Chronic liver failure (Child Pugh score: C)

N. have evidence of infection by gram-positive bacteria, fungal infection, or mixed infection

O. have chosen palliative care and signed Do Not Resuscitate sheet

P. an APACHE II score over 30 present on entry into the trial

Q. non-native speakers

  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: NCT01756755

Contacts
Contact: Yu-Chang Yeh, M.D., Ph.D. 886-9-10513711 tonyyeh@ntuh.gov.tw

Locations
Taiwan
Taipei Tzu Chi General Hospital Not yet recruiting
New Taipei, Taiwan, 231
Contact: Che-Hsiung Wu, MD    886-9-70351817    tcubear@tzuchi.com.tw   
Principal Investigator: Che-Hsiung Wu, MD         
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Yu-Chang Yeh, M.D., Ph.D.    886-9-10513711    tonyyeh@ntuh.gov.tw   
Principal Investigator: Yu-Chang Yeh, M.D., Ph.D.         
Taipei Medical University Hospital Not yet recruiting
Taipei, Taiwan, 110
Contact: Chih-Chin Kao, MD    886-9-37857150    salmonkao@gmail.com   
Principal Investigator: Chih-Chin Kao, MD         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Yu-Chang Yeh, M.D., Ph.D. National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01756755     History of Changes
Other Study ID Numbers: 201208067RIB
Study First Received: December 20, 2012
Last Updated: July 23, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Sepsis

Additional relevant MeSH terms:
Sepsis
Infection
Inflammation
Pathologic Processes
Systemic Inflammatory Response Syndrome

ClinicalTrials.gov processed this record on October 29, 2014