Endotoxin Adsorber Hemoperfusion and Microcirculation

NCT01756755 | Completed DMC

• 1 other identifier: 201208067RIB
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Sepsis

Keywords

Sepsis

Outcome Measures

Primary Outcomes (1)

• Total small vessel density of sublingual microcirculation

  48h

Secondary Outcomes (1)

• Change of SOFA score

  48h

Other Outcomes (1)

• Number of participates die within 28 days

  28 days

Study Arms (2)

Control

NO INTERVENTION

Treat with severe sepsis / septic shock practice guideline

PMX HP

EXPERIMENTAL

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

Interventions

PMX-20R Hemoperfusion DEVICE

Polymyxin B adsorbs and remove endotoxin from the patient's circulating blood.

PMX HP

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included in this study if they meet the following criteria (A+B+C):
• A. Patients with the following conditions:
• Abdominal cavity infection following emergency surgery.
• 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 :
• Fever or hypothermia (body temperature over 38 ℃ or under 36 ℃)
• Tachycardia (heart rate \> 90 bpm)
• Tachypnea (respiratory rate over 20 breaths/min or under mechanical ventilation)
• 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:
• 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.
• Acute lung injury: PaO2 / FiO2 ratio less than 300 (ratio in mm Hg)
• 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.
• Acute liver injury: Total bilirubin level more than 4 mg/dL
• Disseminated intravascular coagulation: platelet count less than 100,000 cells/mm3 or a reduction of more than 50 % of baseline

You may not qualify if:

• 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
• chronic respiratory failure ( COPD at last stage)

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (3)

Taipei Tzu Chi General Hospital

New Taipei City, 231, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Medical University Hospital

Taipei, 110, Taiwan

Location

Related Publications (1)

• Chen SH, Chan WS, Liu CM, Chiu CT, Chao A, Wu VC, Sheng WH, Lai CH, Wang MJ, Yeh YC. Effects of endotoxin adsorber hemoperfusion on sublingual microcirculation in patients with septic shock: a randomized controlled trial. Ann Intensive Care. 2020 Jun 12;10(1):80. doi: 10.1186/s13613-020-00699-z.

  PMID: 32533380 DERIVED

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yu-Chang Yeh, M.D., Ph.D.

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2012
• First Posted: December 27, 2012
• Study Start: December 1, 2012
• Primary Completion: August 1, 2018
• Study Completion: June 1, 2019
• Last Updated: June 11, 2019

Record last verified: 2019-06

Locations

TW (3)