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

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.

Study Overview

• Status: Unknown
• Conditions: Mechanical Ventilation Complication; Ventilator-associated Bacterial Pneumonia
• Intervention / Treatment: Drug: placebo; Drug: Ulinaststin for injection

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 .

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 201199
    • Shanghai Minhang Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of inflammatory factors in bronchoalveolar lavage fluid and blood serum.	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.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality.		30 days
Ventilation free days.		30 days
Antibiotic free days.		30 days
Percentage of MDR pathogenic bacteria.	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.	30 days
Oxygenation index	Oxygenation index = Fio2/PaO2(mmHg)	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects	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.	30 days

Collaborators and Investigators

• Sponsor: Shanghai Minhang Central Hospital
• Collaborators: RenJi Hospital; Ruijin Hospital; Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ANTICIPATED): December 1, 2015
• Study Completion (ANTICIPATED): June 1, 2016

Study Registration Dates

• First Submitted: May 24, 2013
• First Submitted That Met QC Criteria: May 29, 2013
• First Posted (ESTIMATE): May 30, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): May 30, 2013
• Last Update Submitted That Met QC Criteria: May 29, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: mechanical ventilation; ventilator-associated pneumonia; inflammatory factors; bronchoalveolar lavage fluid; ulinastatin for injection
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: VAP-YYT-003