The Efficacy and Safety of Ta1 for Sepsis

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

Detailed Description
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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.

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

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Thymosin alpha 1
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤85; Signed informed consent signed; 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; Infected focus are confirmed or suspected and satisfy at least one of the followings: pathogenic microbes grow in blood or at aseptic locations presence of abscess or partially-infected tissues 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: History of organ or bone marrow transplantation; Acute phase connective tissue diseases (such as rheumatoid diseases, systemic lupus erythematosus) and glomerulonephritis; Under pregnancy or in suckling period; Presence of hematologic malignancies; The patient has received radiotherapy or chemotherapy within the past 30 days; The patient is inclined to stop or cancel the artificial intervention for sustaining life, in other words, has abandoned treatment; 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); The patient could die of an underlying disease within 28 days or is in end-stage; The patient has undergone CPR in the 72 hours before signing the informed consent and the neuromechanism has not fully recovered (GCS score ≤ 8); 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); The patient has a medical history of allergy or intolerance to thymalfasin; The source of infection cannot be contained, for example: infections that cannot be handled during surgical operations and drainage.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: thymosin alpha 1<br>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<br>* 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.<br>* Other names: thymalfasin;|
| Placebo Comparator: Placebo<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of new onset infection within 28 days | from initial injection on day 0 to day 28 | 28 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 | 
| ICU 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 | 
| The percentage of Treg cells at screening and days 7 |  | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thymosin alpha 1; thymalfasin; sepsis; immunodepression