The Efficacy and Safety of Ta1 for Sepsis (TESTS)

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

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

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Drug: Thymosin alpha 1; Other: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 1106
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Friendship Hospital, Capital Medical University
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100000
      • Chinese PLA General Hospital
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • The First People's Hospital of Foshan
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    • Guangzhou, Guangdong, China, 510000
      • Guangzhou First People's Hospital
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510000
      • The Sixth Affiliated Hospital of Sun Yat-sen University
    • Qingyuan, Guangdong, China
      • Qingyuan People's Hospital
    • Shenzhen, Guangdong, China
      • Peking University Shenzhen Hospital
    • Zhuhai, Guangdong, China
      • Zhuhai People's Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Nanjing General Hospital of Nanjing Military Commend
  • Shaanxi
    • Xi'an, Shaanxi, China
      • The First Affiliated Hospital of Xi 'an Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250014
      • Shandong Provincial Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Shanghai Ruijin Hospital
    • Shanghai, Shanghai, China, 200000
      • Shanghai Zhongshan Hospital, Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • West China Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China, 310000
      • The second affiliated hospital of zhejiang university school of medicine
    • Hangzhou, Zhejiang, China, 310000
      • Zhejiang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: thymosin alpha 1; 1ml subcutaneous injection with 1.6 mg thymosin alpha 1, every 12±2 hours for not more than 7 days depending on the change of the subjects' condition	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 Names: thymalfasin
Placebo Comparator: Placebo; 1ml subcutaneous injection with placebo, every 12±2 hours for not more than 7 days depending on the change of the subjects' condition	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
28-day all-cause mortality	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU mortality		90 days
28-day clearance rate of pathogenic microorganism		28 days
ICU stays		90 days
Hospital stays		28 days
28-day re-hospitalization rate		28 days
Changes of SOFA score at screening, end of CTM, days 7 (if applicable), day 14 and day 28		28 days
90-day all-cause mortality		90 days
Ventilator-free days within 28 days		28 days
ICU-free days within 28 days		28 days
CRRT-free days within 28 days		28 days
Vasoactive agents-free days within 28 days		28 days
90-day SF-36 QOL scale		90 days
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
Incidence of new onset infection within 28 days	from initial injection on day 0 to day 28	28 days
The percentage of Treg cells at screening and days 7		7 days

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: SciClone Pharmaceuticals

Publications and helpful links

General Publications

• 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 trial. Crit Care. 2013 Jan 17;17(1):R8. doi: 10.1186/cc11932.
• 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/annals.1415.002. Epub 2007 May 10.
• 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.
• 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: 10.1007/s10753-010-9224-1. Erratum In: Inflammation. 2011 Jun;34(3):222-3.

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2016
• Primary Completion (Actual): January 22, 2021
• Study Completion (Actual): March 23, 2021

Study Registration Dates

• First Submitted: August 10, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (Estimate): August 15, 2016

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: thymosin alpha 1; thymalfasin; sepsis; immunodepression
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Thymalfasin
• Other Study ID Numbers: ZDX-2015-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No