The Efficacy and Safety of Ta1 for Sepsis

Sepsis Clinical Trial

— TESTS  

Official title:

The Efficacy and Safety of Thymosin Alpha 1 for Sepsis: a Multicenter , Double-Blinded, Randomized and Controlled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02867267
• Other study ID #: ZDX-2015-11
• Status: Completed
• Phase: Phase 3
• Start date: September 6, 2016
• Est. completion date: March 23, 2021

Study information

• Verified date: April 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether thymalfasin is safe and effective in patients who have sepsis

Description:

Our previous study reported that the 7-day treatment of Ta 1 demonstrated positive active effect as to the 28-day all-cause mortality and the augmentation of mHLA-DR (monocyte Human Leukocyte Antigen DR) at the secondary endpoint. Therefore, we intend to verify this finding through a randomized, double-blind and placebo-controlled clinical trial and the trail will include subjects with impaired immunologic functions.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1106
• Est. completion date: March 23, 2021
• Est. primary completion date: January 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Age = 18 and =85;

2. Signed informed consent signed;

3. Diagnosed as a sepsis according to the sepsis diagnosis criteria in "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016": at least one acute severe organ dysfunction related to sepsis, and total SOFA scores =2;

4. Infected focus are confirmed or suspected and satisfy at least one of the followings:

1. pathogenic microbes grow in blood or at aseptic locations

2. presence of abscess or partially-infected tissues

3. suspected infection identified by at least one of the following evidences:

• leukocytes at normal aseptic locations
• organic perforation (confirmed by imaging evidence, examination result or intestinal content leak during drainage)
• Imaging evidence of pneumonia accompanied by purulent secretion
• Related syndromes with high infection risk (cholangitis for example)

Exclusion Criteria:

1. History of organ or bone marrow transplantation;

2. Acute phase connective tissue diseases (such as rheumatoid diseases, systemic lupus erythematosus) and glomerulonephritis;

3. Under pregnancy or in suckling period;

4. Presence of hematologic malignancies;

5. The patient has received radiotherapy or chemotherapy within the past 30 days;

6. The patient is inclined to stop or cancel the artificial intervention for sustaining life, in other words, has abandoned treatment;

7. The patient has in the past 30 days received immunosuppressive drugs (tripterygium wilfordii, CellCept, cyclophosphamide, FK506, etc.) or received continuous treatment with prednisolone >10 mg/day (or the same dose of other hormones);

8. The patient could die of an underlying disease within 28 days or is in end-stage;

9. The patient has undergone CPR in the 72 hours before signing the informed consent and the neuromechanism has not fully recovered (GCS score = 8);

10. The patient has in the past 30 days used thymosin or undergone certain clinical drug or instrument trials which could affect immunity (such as Xuebijing, ulinastatin and CRRT);

11. The patient has a medical history of allergy or intolerance to thymalfasin;

12. The source of infection cannot be contained, for example: infections that cannot be handled during surgical operations and drainage.

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Drug:
• Thymosin alpha 1
Subcutaneous injections of 1.6 mg thymosin alpha 1 every 12±2 hours for not more than 7 days depending on the change of the subjects' condition, prior to administration, the lyophilized powder is to be reconstituted with 1 ml of the provided diluent.

Other:
• Placebo
Subcutaneous injections of placebo every 12±2 hours for not more than 7 days depending on the change of the subjects' condition, prior to administration, the lyophilized powder is to be reconstituted with 1 ml of the provided diluent.

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The First People's Hospital of Foshan	Foshan	Guangdong
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The Sixth Affiliated Hospital of Sun Yat-Sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Hospital	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Shandong Provincial Hospital	Jinan	Shandong
China	Nanjing General Hospital of Nanjing Military Commend	Nanjing	Jiangsu
China	Qingyuan People's Hospital	Qingyuan	Guangdong
China	Shanghai Ruijin Hospital	Shanghai	Shanghai
China	Shanghai Zhongshan Hospital, Fudan University	Shanghai	Shanghai
China	Peking University Shenzhen Hospital	Shenzhen	Guangdong
China	Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xi 'an Jiaotong University	Xi'an	Shaanxi
China	Zhuhai People's Hospital	Zhuhai	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	SciClone Pharmaceuticals

Country where clinical trial is conducted

China, 

References & Publications (4)

Romani L, Bistoni F, Montagnoli C, Gaziano R, Bozza S, Bonifazi P, Zelante T, Moretti S, Rasi G, Garaci E, Puccetti P. Thymosin alpha1: an endogenous regulator of inflammation, immunity, and tolerance. Ann N Y Acad Sci. 2007 Sep;1112:326-38. doi: 10.1196/ — View Citation

Romani L, Moretti S, Fallarino F, Bozza S, Ruggeri L, Casagrande A, Aversa F, Bistoni F, Velardi A, Garaci E. Jack of all trades: thymosin alpha1 and its pleiotropy. Ann N Y Acad Sci. 2012 Oct;1269:1-6. doi: 10.1111/j.1749-6632.2012.06716.x. — View Citation

Wang X, Li W, Niu C, Pan L, Li N, Li J. Thymosin alpha 1 is associated with improved cellular immunity and reduced infection rate in severe acute pancreatitis patients in a double-blind randomized control study. Inflammation. 2011 Jun;34(3):198-202. doi: — View Citation

Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, Chen J, Ou-Yang B, Chen M, Li Y, Wu X, Gu B, Chen L, Zou Z, Qiang X, Chen Y, Lin A, Zhang G, Guan X. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28-day all-cause mortality		28 days
Secondary	Incidence of new onset infection within 28 days	from initial injection on day 0 to day 28	28 days
Secondary	28-day clearance rate of pathogenic microorganism		28 days
Secondary	ICU stays		90 days
Secondary	Hospital stays		28 days
Secondary	28-day re-hospitalization rate		28 days
Secondary	Changes of SOFA score at screening, end of CTM, days 7 (if applicable), day 14 and day 28		28 days
Secondary	90-day all-cause mortality		90 days
Secondary	ICU mortality		90 days
Secondary	Ventilator-free days within 28 days		28 days
Secondary	ICU-free days within 28 days		28 days
Secondary	CRRT-free days within 28 days		28 days
Secondary	Vasoactive agents-free days within 28 days		28 days
Secondary	90-day SF-36 QOL scale		90 days
Secondary	Variance of the count of monocyte human lymphocyte antigens-DR (mHLA-DR) at days 7, 14 and 28 compared with the baseline at screening		28 days
Secondary	The percentage of Treg cells at screening and days 7		7 days