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

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)

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.

Study Overview

• Status: Unknown
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: ulinastatin; Drug: placebo

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．

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • The First Affiliated Hospital of Bengbu Medical College
  • Beijing
    • Beijing, Beijing, China, 100029
      • Beijing Anzhen Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
    • Guangzhou, Guangdong, China
      • First Affiliated Hospital of Guangzhou Medical University
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huadong Hospital,Fudan University
  • Shanghia
    • Shanghai, Shanghia, China, 200233
      • Shanghai Sixth People's Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital,Sichuan Unversity
  • Xinjiang
    • Urumqi, Xinjiang, China, 830054
      • The first affiliated hospital of Xinjiang medical university
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310030
      • Zhejiang Hospital
    • Lishui, Zhejiang, China, 323000
      • Lishui City People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Cohort 1- Ulinastatin 4.8 million units per day	Drug: ulinastatin; Patients will receive the study drugs for 7 to 14 days; Other Names: UTI; urinary trypsin inhibitor; bikunin
Experimental: Cohort 2; Cohort 2- Ulinastatin 2.4 million units per day	Drug: ulinastatin; Patients will receive the study drugs for 7 to 14 days; Other Names: UTI; urinary trypsin inhibitor; bikunin
Experimental: Cohort 3; Cohort 3- Ulinastatin 1.2 million units per day	Drug: ulinastatin; Patients will receive the study drugs for 7 to 14 days; Other Names: UTI; urinary trypsin inhibitor; bikunin
Placebo Comparator: control group; Placebo	Drug: placebo; Patients will receive the placebo for 7 to 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Techpool Bio-Pharma Co., Ltd.
• Collaborators: The First Affiliated Hospital of Guangzhou Medical University
• Investigators: Principal Investigator: Yimin Li, Doctor, First Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: July 21, 2016
• First Submitted That Met QC Criteria: September 5, 2016
• First Posted (Estimate): September 9, 2016

Study Record Updates

• Last Update Posted (Actual): April 20, 2018
• Last Update Submitted That Met QC Criteria: April 19, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Urinastatin; Trypsin Inhibitors
• Other Study ID Numbers: UTI-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided