Clinical trial NCT02895191: The Safety and Dose Response Relationship of Ulinastatin for Acute Respiratory Distress Syndrome(ARDS)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome
Lead sponsor: Techpool Bio-Pharma Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Guangzhou Medical University
First posted: 2016-09-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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．

Eligibility criteria: Inclusion Criteria:

1. Have provided signed written informed consent form (ICF) from the patient or the patient's legal representative;
2. Male or Female patients ≥18 years of age;
3. ARDS defined with using 2012 Berlin Criteria;
4. 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:

1. Patient with known hypersensitivity to Ulinastatin/adjuvant or patient with allergic constitution;
2. Patients with artificial organs replacement therapy for liver or kidney；
3. Glasgow Coma Scale (GCS)≤8；
4. Cardiogenic pulmonary edema , and the cardiogenic pulmonary edema is as the only or primary reason for respiratory failure;
5. ARDS caused by burning, drowning, poisoning;
6. 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;
7. Neutrophils\<1.5×10\^9/L
8. Moribund patients (i.e.,expected to live no longer than 24 hours) or with recent (within 7days or anytime during present hospitalization) cardiopulmonary arrest;
9. Patients need long-term glucocorticoid treatment or need to be treated with immunosuppressive drugs;
10. No intent/unwillingness to follow lung protective ventilation strategy or fluid management protocol;
11. Lung transplant patients;
12. Patients with malignancy, expected to live no longer than 6 months;
13. Pregnant or breast-feeding;
14. Patients who have participated in any clinical study within 3 months prior to the screening;
15. Any condition that in the opinion of the investigator would add the patient's risk or jeopardize the operation of the study.

Primary outcomes:
measure: The incidence of adverse events(AEs) which can not excluded relatedness with study Product
timeFrame: Day 1 to Day 90
Secondary outcomes:
measure: Changes of PaO2/FiO2 ratio
timeFrame: Day 0 and Day 1 to within 24h after the last treatment
measure: Days alive and off ventilator
timeFrame: Day 1 to Day 28
measure: Days in the ICU
timeFrame: Day 1 to Day 14
measure: Changes of pulmonary compliance
timeFrame: Day 1 , Day 3 ,Day7 and within 24h after the last treatment
measure: Rate of new organ failure
timeFrame: Day 1 to Day 90
measure: Changes of APACHEⅡ Score from baseline
timeFrame: Day 3 ,Day7 and within 24h after the last treatment
measure: Changes of Murray Lung Injury Score from baseline
timeFrame: Day 3 ,Day7 and within 24h after the last treatment
measure: Changes of Sequential Organ Failure Assessment (SOFA) score from baseline
timeFrame: Day 3 ,Day7 and within 24h after the last treatment
measure: All-cause mortality
timeFrame: Day 28 , Day 90 and Day 1 to Day 14
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Anzhen Hospital, Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Shanghai
country: China
facility: Huadong Hospital,Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghia
city: Chengdu
country: China
facility: West China Hospital,Sichuan Unversity
state: Sichuan
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: Zhejiang Hospital
state: Zhejiang
city: Lishui
country: China
facility: Lishui City People's Hospital
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Guangzhou Medical University
name: Yimin Li, Doctor
role: PRINCIPAL_INVESTIGATOR
References: