The Safety and Dose Response Relationship of Ulinastatin for Acute Respiratory Distress Syndrome(ARDS)

Study Overview
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Brief Summary
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Compared with placebo, evaluate the effects and safety of Ulinastatin(UTI) added to conventional treatment for ARDS; Evaluate the dose response relationship of Ulinastatin for ARDS.

Detailed Description
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After signed off the informed consent form by patient or surrogate, and after completing the screening phase, the patients who fulfill the inclusion and exclusion criteria will be randomized 1:1:1:1 to the 4 study arms. All the Patients will receive the study treatment drugs for 7 to 14 days. Use Day 28 of last patient as a cut-off day, Collect the follow up visit data on both Day 28 and Day 90 of other patients．

Official Title
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A Randomized, Blind, Placebo-controlled, Parallel Group, Multi-center Study to Evaluate the Safety and Dose Response Relationship of Ulinastatin for Acute Respiratory Distress Syndrome(ARDS)

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: ulinastatin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have provided signed written informed consent form (ICF) from the patient or the patient's legal representative; Male or Female patients ≥18 years of age; ARDS defined with using 2012 Berlin Criteria; ARDS diagnosed ≤7 days, and patients should be mechanically ventilated(invasive and or noninvasive mechanical ventilation); 5)100mmhg < PaO2/FiO2 < 250mmhg with CPAP/PEEP≥5 cmH2O; Exclusion Criteria: Patient with known hypersensitivity to Ulinastatin/adjuvant or patient with allergic constitution; Patients with artificial organs replacement therapy for liver or kidney； Glasgow Coma Scale (GCS)≤8； Cardiogenic pulmonary edema , and the cardiogenic pulmonary edema is as the only or primary reason for respiratory failure; ARDS caused by burning, drowning, poisoning; Presence of severe chronic liver diseases (Child-Pugh score 12-15)，or severe chronic respiratory disease with a PaCO2 > 50 mmHg or the use of home oxygen; Neutrophils<1.5×10^9/L Moribund patients (i.e.,expected to live no longer than 24 hours) or with recent (within 7days or anytime during present hospitalization) cardiopulmonary arrest; Patients need long-term glucocorticoid treatment or need to be treated with immunosuppressive drugs; No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol; Lung transplant patients; Patients with malignancy, expected to live no longer than 6 months; Pregnant or breast-feeding; Patients who have participated in any clinical study within 3 months prior to the screening; Any condition that in the opinion of the investigator would add the patient's risk or jeopardize the operation of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1- Ulinastatin 4.8 million units per day | Drug: ulinastatin<br>* Patients will receive the study drugs for 7 to 14 days<br>* Other names: bikunin;|
| Experimental: Cohort 2<br>Cohort 2- Ulinastatin 2.4 million units per day | Drug: ulinastatin<br>* Patients will receive the study drugs for 7 to 14 days<br>* Other names: bikunin;|
| Experimental: Cohort 3<br>Cohort 3- Ulinastatin 1.2 million units per day | Drug: ulinastatin<br>* Patients will receive the study drugs for 7 to 14 days<br>* Other names: bikunin;|
| Placebo Comparator: control group<br>Placebo | Drug: placebo<br>* Patients will receive the placebo for 7 to 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events(AEs) which can not excluded relatedness with study Product |  | Day 1 to Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of PaO2/FiO2 ratio |  | Day 0 and Day 1 to within 24h after the last treatment | 
| Days alive and off ventilator |  | Day 1 to Day 28 | 
| Days in the ICU |  | Day 1 to Day 14 | 
| Changes of pulmonary compliance |  | Day 1 , Day 3 ,Day7 and within 24h after the last treatment | 
| Rate of new organ failure |  | Day 1 to Day 90 | 
| Changes of APACHEⅡ Score from baseline |  | Day 3 ,Day7 and within 24h after the last treatment | 
| Changes of Murray Lung Injury Score from baseline |  | Day 3 ,Day7 and within 24h after the last treatment | 
| Changes of Sequential Organ Failure Assessment (SOFA) score from baseline |  | Day 3 ,Day7 and within 24h after the last treatment | 
| All-cause mortality |  | Day 28 , Day 90 and Day 1 to Day 14 |