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

Mechanical Ventilation Complication Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01865266
• Other study ID #: VAP-YYT-003
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• First received: May 24, 2013
• Last updated: May 29, 2013
• Start date: January 2014
• Est. completion date: June 2016

Study information

• Verified date: May 2013
• Source: Shanghai Minhang Central Hospital
• Contact: Yu YueTian, MD
• Phone: 13818227011
• Email: fishyyt[@]sina.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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 .

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: June 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mechanical Ventilation Complication
• Pneumonia
• Pneumonia, Bacterial
• Pneumonia, Ventilator-Associated
• Ventilator-associated Bacterial Pneumonia

Intervention

Drug:
• Ulinaststin for injection

• placebo

Locations

Country	Name	City	State
China	Shanghai Minhang Central Hospital	Shanghai

Sponsors (4)

Lead Sponsor	Collaborator
Shanghai Minhang Central Hospital	RenJi Hospital, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Primary	Levels of inflammatory factors in bronchoalveolar lavage fluid and blood serum.	The variety of tumor necrosis factor-a(TNF-a),interleukin-10(IL-10),interleukin-18(IL-18) and interferon-?(INF-?) in bronchoalveolar lavage fluid and blood serum are observed.	7 days	Yes
Secondary	All cause mortality.		30 days	Yes
Secondary	Ventilation free days.		30 days	Yes
Secondary	Antibiotic free days.		30 days	Yes
Secondary	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	Yes
Secondary	Oxygenation index	Oxygenation index = Fio2/PaO2(mmHg)	30 days	Yes