Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS)

NCT ID: NCT03089957

Last Updated: 2024-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 840 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-20
• Study Completion Date: 2021-07-01

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.

Conditions

Acute Respiratory Distress Syndrome; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Ulinastatin group

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.

Group Type: EXPERIMENTAL

Ulinastatin

Intervention Type: DRUG

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.

Usual care

Intervention Type: OTHER

Usual care in ICU.

Control group

Control group will be in usual care without any intervention.

Group Type: PLACEBO_COMPARATOR

Usual care

Intervention Type: OTHER

Usual care in ICU.

Interventions

Ulinastatin

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: DRUG

Usual care

Usual care in ICU.

Intervention Type: OTHER

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: collaborator

Peking University Shenzhen Hospital

OTHER

Sponsor Role: collaborator

Central Hospital of Zi Bo

UNKNOWN

Sponsor Role: collaborator

Beijing Anzhen Hospital

OTHER

Sponsor Role: collaborator

The Second Affiliated Hospital of Dalian Medical University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Guangxi Medical University

OTHER

Sponsor Role: collaborator

Beijing Shijitan Hospital Affiliated to Capital Medical University

UNKNOWN

Sponsor Role: collaborator

Peking University Third Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhu Xi

M.D. Chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xi Zhu, M.D.

Role: PRINCIPAL_INVESTIGATOR

Peking University Third Hospital

Locations

Peking University Third Hospital

Beijing, Beijing Municipality, China

Beijing Anzhen Hospital ,Capital Medical University

Beijing, Beijing Municipality, China

Beijing Shijitan Hospital Affiliated to Capital Medical University

Beijing, Beijing Municipality, China

Chinese Pla General Hospital

Beijing, Beijing Municipality, China

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

The first affiliated hospital of Guangxi Medical University

Nanning, Guangxi, China

CANGZHOU People's Hospital

Cangzhou, Hebei, China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

The second hospital of dalian medical university

Dalian, Liaoning, China

Central Hospital of Zi Bo

Zibo, Shandong, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 22949978 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22797452 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23782966 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18203972 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30850411 (View on PubMed)

Other Identifiers

2016-0001

Identifier Type: -

Identifier Source: org_study_id