Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS)

Critical Illness Clinical Trial

Official title:

Prevention of Ulinastatin on Acute Respiratory Distress Syndrome (ARDS) A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03089957
• Other study ID #: 2016-0001
• Status: Completed
• Phase: N/A
• Start date: February 20, 2017
• Est. completion date: July 1, 2021

Study information

• Verified date: January 2024
• Source: Peking University Third Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 840
• Est. completion date: July 1, 2021
• Est. primary completion date: December 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Critical Illness
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• 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.

Other:
• Usual care
Usual care in ICU.

Locations

Country	Name	City	State
China	Beijing Anzhen Hospital ,Capital Medical University	Beijing	Beijing
China	Beijing Shijitan Hospital Affiliated to Capital Medical University	Beijing	Beijing
China	Chinese Pla General Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	CANGZHOU People's Hospital	Cangzhou	Hebei
China	The second hospital of dalian medical university	Dalian	Liaoning
China	The first affiliated hospital of Guangxi Medical University	Nanning	Guangxi
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Central Hospital of Zi Bo	Zibo	Shandong

Sponsors (9)

Lead Sponsor	Collaborator
Peking University Third Hospital	Beijing Anzhen Hospital, Beijing Shijitan Hospital Affiliated to Capital Medical University, Central Hospital of Zi Bo, Chinese PLA General Hospital, First Affiliated Hospital of Guangxi Medical University, Peking University Shenzhen Hospital, The First Affiliated Hospital of Zhengzhou University, The Second Affiliated Hospital of Dalian Medical University

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	Including white blood cell decrease, eosinophils increase, nausea, vomiting, diarrhoea, liver enzymes increase, allergy, adverse events in injection sites and etc.	3 years
Primary	The incidence of ARDS		3 years
Secondary	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.	3 years
Secondary	The number of patients who need mechanical ventilation		3 years
Secondary	Lengths of mechanical ventilation		3 years
Secondary	Lengths of ICU		3 years
Secondary	Lengths of stay		3 years
Secondary	The incidence of other organ disorders		3 years
Secondary	Mortality of 28 days		0-28 days
Secondary	Mortality of 60 days		0-60 days
Secondary	Total cost in admission		3 years
Secondary	Adverse events related to drugs.		3 years