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The Effect of Ulinastatin on Bronchoalveolar Lavage Fluid of Inflammatory Factors in Patients With Ventilator-associated Pneumonia

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified May 2013 by Yu YueTian, Shanghai Minhang Central Hospital.
Recruitment status was:  Not yet recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01865266
First Posted: May 30, 2013
Last Update Posted: May 30, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Ruijin Hospital
RenJi Hospital
Shanghai Jiao Tong University School of Medicine
Information provided by (Responsible Party):
Yu YueTian, Shanghai Minhang Central Hospital
  Purpose

Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality in ventilated critically ill patients specially in intensive care unit (ICU). It is associated with an increased duration of mechanical ventilation, high death rates and increased healthcare costs in the development country.

Although VAP is preventable and many practices have been demonstrated to reduce the incidence of this disease, the morbidity is still so high. VAP is hard to cure and the mortality is about to 40% which was reported in China in 2004. If the bacteria of multidrug-resistance(MDR) is isolated, the mortality can increase to 70%. So much more methods should be needed in treating VAP in addition to using antibiotics.

Ulinastatin is a serine protease inhibitor with a molecular weight of 67,000 found in healthy human urine. It is used worldwide for patients with inflammatory disorders, including disseminated intravascular coagulation(DIC),shock, and pancreatitis . Furthermore, ulinastatin administration can help reduce sepsis, prevent multiple organ dysfunction, and modulate immune functions.

Actually, three studies have showed that ulinastatin treatment is associated with reduced the levels of inflammatory factors in blood serum in patients with acute respiratory distress syndrome(ARDS).Though analyses of serum inflammatory factors such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 have been used to determine the degree of systemic inflammation under various clinical conditions, they can not reflect the degrees of lung infection directly.

Basing on the results of previous studies, meta analyses and system reviews, the investigators hypothesized that the anti-inflammatory function of ulinaststin may also decrease the levels of inflammatory factors in bronchoalveolar lavage(BAL) fluid in Patients with VAP.

In addition there is no prospective study to investigate the role of ulinastatin in BAL. The investigator hopes that this study can approve the relationship between ulinastatin and inflammatory factors in BAL. And it can improve the processes,outcomes and costs of critical care as well.


Condition Intervention Phase
Ventilator-associated Bacterial Pneumonia Mechanical Ventilation Complication Drug: Ulinaststin for injection Drug: placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: The Effect of Ulinastatin on Bronchoalveolar Lavage Fluid of Inflammatory Factors in Patients With Ventilator-associated Pneumonia

Resource links provided by NLM:


Further study details as provided by Yu YueTian, Shanghai Minhang Central Hospital:

Primary Outcome Measures:
  • Levels of inflammatory factors in bronchoalveolar lavage fluid and blood serum. [ Time Frame: 7 days ]
    The variety of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),interleukin-18(IL-18) and interferon-γ(INF-γ) in bronchoalveolar lavage fluid and blood serum are observed.


Secondary Outcome Measures:
  • All cause mortality. [ Time Frame: 30 days ]
  • Ventilation free days. [ Time Frame: 30 days ]
  • Antibiotic free days. [ Time Frame: 30 days ]
  • Percentage of MDR pathogenic bacteria. [ Time Frame: 30 days ]

    We will find whether the bacteria of multidrug-resistance can be isolated from the bronchoalveolar lavage fluid culture.

    We will count the number of methicillin-resistant staphylococcus aureus(MRSA),extended-spectrum beta-lactamase(ESBLs) or vancomycin-resistant enterococcus(VRE) isolated from bronchoalveolar lavage fluid culture.


  • Oxygenation index [ Time Frame: 30 days ]
    Oxygenation index = Fio2/PaO2(mmHg)


Other Outcome Measures:
  • Adverse effects [ Time Frame: 30 days ]
    The adverse effects from using ulinastatin. Irritability,nausea,vomit,diarrhoea or the aspartate transaminaseere and alanine transaminase are more than one time the upper normal limit were regarded as the adverse effects.


Estimated Enrollment: 60
Study Start Date: January 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NUTIG

The normal dose of ulinastatin for injection group(NUTIG):

Ulinastatin(Techpool inc,Guangdong,China) was administered to the group as a bolus of 100,000 U diluted in 100 mL of normal saline every 8 hour.A course of treatment consisted of 7 days after the patients were diagnosed as VAP.

Drug: Ulinaststin for injection
Experimental: HUTIG

The high dose of ulinastatin for injection group(HUTIG):

Ulinastatin(Techpool inc,Guangdong,China) was administered to the group as a bolus of 200,000 U diluted in 100 mL of normal saline every 8 hour.A course of treatment consisted of 7 days after the patients were diagnosed as VAP.

Drug: Ulinaststin for injection
Placebo Comparator: CG

The compare group(CG):

The group was given 100 mL of normal saline every 8 hour.A course of treatment consisted of 7 days after the patients were diagnosed as VAP.

Drug: placebo

Detailed Description:

This is a one-center, three-arm, randomized, single-blinded, controlled trial. When a patient was diagnosed VAP during mechanic ventilation in ICU,a sealed envelop will be opened which decide whether the patient is assigned to the normal dose ulinastatin group,the high dose ulinastatin group or the compare group.

VAP diagnosis and treatment accord with the "Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia:Diagnosis and treatment" which was published in 2008 by Canadian critical care trials group.

The aim of the present study is to determine the efficacy of ulinastatin for the treatment of ventilator-associated Pneumonia(VAP) and to investigate the effect to inflammatory factors in bronchoalveolar lavage fluid .

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All consecutive patients with ventilator-associated pneumonia(VAP) who are admitted to the intensive care unit between 1st January 2014 at 0:00(midnight) and the finish date of 31st December 2015 at 23:59 (11:59 pm).
  • Informed consent.

Exclusion Criteria:

  • Patients with pneumonia when they are admitted to ICU.
  • Ulinastatin was previous used before the patients were diagnosed VAP.
  • Active gastropathic disorder.
  • Be allergic to ulinastatin.
  • Pregnancy.
  • Unwilling to continue the therapy during hospitalization.
  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): NCT01865266


Contacts
Contact: Yu YueTian, MD 13818227011 fishyyt@sina.com
Contact: Liu ChunYan, MD 13917836226 doctorlcy@sina.com

Locations
China
Shanghai Minhang Central Hospital Not yet recruiting
Shanghai, China, 201199
Contact: Yu YueTian, MD    13818227011    fishyyt@sina.com   
Contact: Liu ChunYan, MD    13917836226    doctorlcy@sina.com   
Principal Investigator: Yu YueTian, MD         
Sub-Investigator: Mao EnQiang, MD         
Sponsors and Collaborators
Shanghai Minhang Central Hospital
Ruijin Hospital
RenJi Hospital
Shanghai Jiao Tong University School of Medicine
  More Information

Responsible Party: Yu YueTian, Shanghai Minhang Central Hospital
ClinicalTrials.gov Identifier: NCT01865266     History of Changes
Other Study ID Numbers: VAP-YYT-003
First Submitted: May 24, 2013
First Posted: May 30, 2013
Last Update Posted: May 30, 2013
Last Verified: May 2013

Keywords provided by Yu YueTian, Shanghai Minhang Central Hospital:
ventilator-associated pneumonia
mechanical ventilation
ulinastatin for injection
bronchoalveolar lavage fluid
inflammatory factors

Additional relevant MeSH terms:
Pneumonia
Pneumonia, Ventilator-Associated
Pneumonia, Bacterial
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Ventilator-Induced Lung Injury
Lung Injury
Bacterial Infections
Urinastatin
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action