Clinical trial NCT03089957: Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS)
Official title: Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS) A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Critical Illness
Keywords: Acute Respiratory Distress Syndrome
Critical Illness
Randomized Controlled Trial
Ulinastatin
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Chinese PLA General Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Peking University Shenzhen Hospital
name: Central Hospital of Zi Bo
name: Beijing Anzhen Hospital
name: The Second Affiliated Hospital of Dalian Medical University
name: First Affiliated Hospital of Guangxi Medical University
name: Beijing Shijitan Hospital Affiliated to Capital Medical University
First posted: 2017-03-24
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Since strategies were applied in intensive care medicine, including low tidal volume ventilation, fluid resuscitation, use of antibiotics, restrictive transfusion strategy and bundle of ventilator therapy, the incidence of Acute Respiratory Distress Syndrome (ARDS) has been decreased recent years. However, the mortality of severe ARDS is still higher to 45%. Few medications did were indicated to be effective in working on development of ARDS. Different with other disease, ARDS were difficult to prevent in its later stage like a domino effect. The medication interventions are all used after ARDS was developed, including ulinastatin. The investigators hypothesized that the key point in failure of medication therapy is the delay timing of medication intervention. If given the preventive strategy, such as ulinastatin, the incidence or the severity of ARDS might be decreased. Therefore this is a randomized controlled trial to test the hypothesis of the preventive effect of ulinastatin in ARDS.

This is a multi-center, randomized, double blinded, placebo controlled study.

Detailed description: Since strategies were applied in intensive care medicine, including low tidal volume ventilation, fluid resuscitation, use of antibiotics, restrictive transfusion strategy and bundle of ventilator therapy, the incidence of Acute Respiratory Distress Syndrome (ARDS) has been decreased recent years. However, the mortality of severe ARDS is still higher to 45%. Few medications did were indicated to be effective in working on development of ARDS. Different with other disease, ARDS were difficult to prevent in its later stage like a domino effect. The medication interventions are all used after ARDS was developed, including ulinastatin. The investigators hypothesized that the key point in failure of medication therapy is the delay timing of medication intervention. If given the preventive strategy, such as ulinastatin, the incidence or the severity of ARDS might be decreased.

Ulinastatin is a urinary trypsin inhibitor (UTI) that inhibits various inflammatory proteases has been widely used in China, Japan, and Korea for the treatment of patients with inflammatory disorders, postoperative organs protection, shock, and pancreatitis.

Therefore this is a randomized controlled trial to test the hypothesis of the preventive effect of ulinastatin in ARDS.

This is a multi-center, randomized, double blinded, placebo controlled study.

Eligibility criteria: Inclusion Criteria:

* Patients should be more than 18 years old
* Patients are expected to living within 72 hours of ICU admission
* Patients' Lung Injury Prediction Score (LIPS) more than 4 and got at least 1 risk factors as below: bacteremia, sepsis or sepsis shock, pneumonia, multiple fractures, pulmonary contusion, aspiration, multiple blood transfusion, severe acute pancreatitis.

Exclusion Criteria: Patients will be excluded when they are

* diagnosed as ARDS
* without written informed consent
* with HIV infection
* with other immunologic deficiency (leukaemia, immune deficiency syndrome, etc)
* with organ transplantation or bone marrow transplantation
* with chronic pulmonary disease (except for Chronic Obstructive Pulmonary Disease (COPD) or asthma)
* with angitis
* with neutropenia (except for secondary to sepsis)
* using granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor
* using asprin or clopidogrel
* using glucocorticoid
* withdrawing treatment
* treated by Xuebijing, thymosin, or intravenous immunoglobulin 1 month before enrollment
* enrolled in other clinical trials 3 months before enrollment
* being pregnancy
* being lactation

Primary outcomes:
measure: The incidence of ARDS
timeFrame: 3 years
Secondary outcomes:
measure: The numbers of ARDS patients who meet the criteria for mild, moderate, and severe using the Berlin Definition, separately.
timeFrame: 3 years
measure: The number of patients who need mechanical ventilation
timeFrame: 3 years
measure: Lengths of mechanical ventilation
timeFrame: 3 years
measure: Lengths of ICU
timeFrame: 3 years
measure: Lengths of stay
timeFrame: 3 years
measure: The incidence of other organ disorders
timeFrame: 3 years
measure: Mortality of 28 days
timeFrame: 0-28 days
measure: Mortality of 60 days
timeFrame: 0-60 days
measure: Total cost in admission
timeFrame: 3 years
measure: Adverse events related to drugs.
timeFrame: 3 years
Other outcomes:
measure: Adverse events
timeFrame: 3 years
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Anzhen Hospital ,Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Shijitan Hospital Affiliated to Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Chinese Pla General Hospital
state: Beijing
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Nanning
country: China
facility: The first affiliated hospital of Guangxi Medical University
state: Guangxi
city: Cangzhou
country: China
facility: CANGZHOU People's Hospital
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Dalian
country: China
facility: The second hospital of dalian medical university
state: Liaoning
city: Zibo
country: China
facility: Central Hospital of Zi Bo
state: Shandong
Study officials:
affiliation: Peking University Third Hospital
name: Xi Zhu, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jeong CW, Lee CS, Lee SH, Jeung HJ, Kwak SH. Urinary trypsin inhibitor attenuates liver enzyme elevation after liver resection. Korean J Anesthesiol. 2012 Aug;63(2):120-3. doi: 10.4097/kjae.2012.63.2.120. Epub 2012 Aug 14.
citation: ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
citation: Levitt JE, Calfee CS, Goldstein BA, Vojnik R, Matthay MA. Early acute lung injury: criteria for identifying lung injury prior to the need for positive pressure ventilation*. Crit Care Med. 2013 Aug;41(8):1929-37. doi: 10.1097/CCM.0b013e31828a3d99.
citation: Wang Z, Beach D, Su L, Zhai R, Christiani DC. A genome-wide expression analysis in blood identifies pre-elafin as a biomarker in ARDS. Am J Respir Cell Mol Biol. 2008 Jun;38(6):724-32. doi: 10.1165/rcmb.2007-0354OC. Epub 2008 Jan 18.
citation: Wang Z, Tao L, Yan Y, Zhu X. Rationale and design of a prospective, multicentre, randomised, conventional treatment-controlled, parallel-group trial to evaluate the efficacy and safety of ulinastatin in preventing acute respiratory distress syndrome in high-risk patients. BMJ Open. 2019 Mar 7;9(3):e025523. doi: 10.1136/bmjopen-2018-025523.