Clinical trial NCT02867267: The Efficacy and Safety of Ta1 for Sepsis
Official title: The Efficacy and Safety of Thymosin Alpha 1 for Sepsis: a Multicenter , Double-Blinded, Randomized and Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sepsis
Keywords: thymosin alpha 1; thymalfasin; sepsis; immunodepression
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: SciClone Pharmaceuticals
First posted: 2016-08-15
Enrollment: 1106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 28-day all-cause mortality
timeFrame: 28 days
Secondary outcomes:
measure: Incidence of new onset infection within 28 days
timeFrame: 28 days
measure: 28-day clearance rate of pathogenic microorganism
timeFrame: 28 days
measure: ICU stays
timeFrame: 90 days
measure: Hospital stays
timeFrame: 28 days
measure: 28-day re-hospitalization rate
timeFrame: 28 days
measure: Changes of SOFA score at screening, end of CTM, days 7 (if applicable), day 14 and day 28
timeFrame: 28 days
measure: 90-day all-cause mortality
timeFrame: 90 days
measure: ICU mortality
timeFrame: 90 days
measure: Ventilator-free days within 28 days
timeFrame: 28 days
measure: ICU-free days within 28 days
timeFrame: 28 days
measure: CRRT-free days within 28 days
timeFrame: 28 days
measure: Vasoactive agents-free days within 28 days
timeFrame: 28 days
measure: 90-day SF-36 QOL scale
timeFrame: 90 days
measure: Variance of the count of monocyte human lymphocyte antigens-DR (mHLA-DR) at days 7, 14 and 28 compared with the baseline at screening
timeFrame: 28 days
measure: The percentage of Treg cells at screening and days 7
timeFrame: 7 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Foshan
country: China
facility: The First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Zhuhai
country: China
facility: Zhuhai People's Hospital
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: Nanjing General Hospital of Nanjing Military Commend
state: Jiangsu
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital, Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Guan Xiangdong, M. D
role: PRINCIPAL_INVESTIGATOR
References:
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 trial. Crit Care. 2013 Jan 17;17(1):R8. doi: 10.1186/cc11932.
citation: 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.
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.
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: 10.1007/s10753-010-9224-1.