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Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS)

Primary Purpose

Acute Respiratory Distress Syndrome, Critical Illness

Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Ulinastatin
Usual care
Sponsored by
Peking University Third Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Respiratory Distress Syndrome focused on measuring Acute Respiratory Distress Syndrome, Critical Illness, Randomized Controlled Trial, Ulinastatin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Peking University Third Hospital
  • Beijing Anzhen Hospital ,Capital Medical University
  • Beijing Shijitan Hospital Affiliated to Capital Medical University
  • Chinese Pla General Hospital
  • Peking University Shenzhen Hospital
  • The first affiliated hospital of Guangxi Medical University
  • CANGZHOU People's Hospital
  • The First Affiliated Hospital of Zhengzhou University
  • The second hospital of dalian medical university
  • Central Hospital of Zi Bo

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ulinastatin group

Control group

Arm Description

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.

Control group will be in usual care without any intervention.

Outcomes

Primary Outcome Measures

The incidence of ARDS

Secondary Outcome Measures

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.
The number of patients who need mechanical ventilation
Lengths of mechanical ventilation
Lengths of ICU
Lengths of stay
The incidence of other organ disorders
Mortality of 28 days
Mortality of 60 days
Total cost in admission
Adverse events related to drugs.

Full Information

First Posted
March 12, 2017
Last Updated
May 10, 2023
Sponsor
Peking University Third Hospital
Collaborators
Chinese PLA General Hospital, The First Affiliated Hospital of Zhengzhou University, Peking University Shenzhen Hospital, Central Hospital of Zi Bo, Beijing Anzhen Hospital, The Second Affiliated Hospital of Dalian Medical University, First Affiliated Hospital of Guangxi Medical University, Beijing Shijitan Hospital Affiliated to Capital Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03089957
Brief Title
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
February 20, 2017 (Actual)
Primary Completion Date
December 17, 2020 (Actual)
Study Completion Date
July 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University Third Hospital
Collaborators
Chinese PLA General Hospital, The First Affiliated Hospital of Zhengzhou University, Peking University Shenzhen Hospital, Central Hospital of Zi Bo, Beijing Anzhen Hospital, The Second Affiliated Hospital of Dalian Medical University, First Affiliated Hospital of Guangxi Medical University, Beijing Shijitan Hospital Affiliated to Capital Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome, Critical Illness
Keywords
Acute Respiratory Distress Syndrome, Critical Illness, Randomized Controlled Trial, Ulinastatin

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
840 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ulinastatin group
Arm Type
Experimental
Arm Description
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.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Control group will be in usual care without any intervention.
Intervention Type
Drug
Intervention Name(s)
Ulinastatin
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Usual care
Intervention Description
Usual care in ICU.
Primary Outcome Measure Information:
Title
The incidence of ARDS
Time Frame
3 years
Secondary Outcome Measure Information:
Title
The numbers of ARDS patients who meet the criteria for mild, moderate, and severe using the Berlin Definition, separately.
Description
The severity of ARDS will be assessed by the Berlin Definition in mild, moderate and severe ARDs according to oxygenation.
Time Frame
3 years
Title
The number of patients who need mechanical ventilation
Time Frame
3 years
Title
Lengths of mechanical ventilation
Time Frame
3 years
Title
Lengths of ICU
Time Frame
3 years
Title
Lengths of stay
Time Frame
3 years
Title
The incidence of other organ disorders
Time Frame
3 years
Title
Mortality of 28 days
Time Frame
0-28 days
Title
Mortality of 60 days
Time Frame
0-60 days
Title
Total cost in admission
Time Frame
3 years
Title
Adverse events related to drugs.
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Adverse events
Description
Including white blood cell decrease, eosinophils increase, nausea, vomiting, diarrhoea, liver enzymes increase, allergy, adverse events in injection sites and etc.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xi Zhu, M.D.
Organizational Affiliation
Peking University Third Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University Third Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100191
Country
China
Facility Name
Beijing Anzhen Hospital ,Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Beijing Shijitan Hospital Affiliated to Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Chinese Pla General Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Peking University Shenzhen Hospital
City
Shenzhen
State/Province
Guangdong
Country
China
Facility Name
The first affiliated hospital of Guangxi Medical University
City
Nanning
State/Province
Guangxi
Country
China
Facility Name
CANGZHOU People's Hospital
City
Cangzhou
State/Province
Hebei
Country
China
Facility Name
The First Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
Country
China
Facility Name
The second hospital of dalian medical university
City
Dalian
State/Province
Liaoning
Country
China
Facility Name
Central Hospital of Zi Bo
City
Zibo
State/Province
Shandong
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
All data will be shared with other researchers in papers.
Citations:
PubMed Identifier
22949978
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.
Results Reference
background
PubMed Identifier
22797452
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.
Results Reference
background
PubMed Identifier
23782966
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.
Results Reference
background
PubMed Identifier
18203972
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.
Results Reference
background
PubMed Identifier
30850411
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.
Results Reference
derived

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Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS)

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