Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS) A Randomized Controlled Trial

Conditions
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Acute Respiratory Distress Syndrome, Critical Illness

Intervention / Treatment
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* Drug: Ulinastatin
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ulinastatin group<br>200,000 IU ulinastatin will be dissolved in 100 mL of 0.9% normal saline by continuous intravenous infusion for 1h, 3 times per day for 5 days. | Drug: Ulinastatin<br>* 200,000 IU ulinastatin will be dissolved in 100 mL of 0.9% normal saline by continuous intravenous infusion for 1h, 3 times per day for 5 days.<br>Other: Usual care<br>* Usual care in ICU.<br>|
| Placebo Comparator: Control group<br>Control group will be in usual care without any intervention. | Other: Usual care<br>* Usual care in ICU.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of ARDS |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The numbers of ARDS patients who meet the criteria for mild, moderate, and severe using the Berlin Definition, separately. | The severity of ARDS will be assessed by the Berlin Definition in mild, moderate and severe ARDs according to oxygenation. | 3 years | 
| The number of patients who need mechanical ventilation |  | 3 years | 
| Lengths of mechanical ventilation |  | 3 years | 
| Lengths of ICU |  | 3 years | 
| Lengths of stay |  | 3 years | 
| The incidence of other organ disorders |  | 3 years | 
| Mortality of 28 days |  | 0-28 days | 
| Mortality of 60 days |  | 0-60 days | 
| Total cost in admission |  | 3 years | 
| Adverse events related to drugs. |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, Critical Illness, Randomized Controlled Trial, Ulinastatin