Clinical Study of Recombinant Mycobacterium Tuberculosis ESAT6-CFP10 Allergen

Study Overview
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Brief Summary
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720 cases TB (Tuberculosis patients) participants、360 cases non-TB participants with lung disease and suspected TB patients who all meet the standard are divided into different groups through a randomized and blind method. Every subject inject intradermally ESAT6-CFP10 and TB-PPD (tuberculin purified protein derivative) in different arms of the same person by blind method. Specific gama-interferon (γ-IFN) detection is needed before the injection.Measure the induration and (or) redness of longitudinal diameter size and transverse diameter vernier caliper by vernier caliper after injection 24h, 48h and 72h. At the same time, we observe all kind of adverse events.

Detailed Description
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Firstly, 720 cases TB (Tuberculosis) participants who meet the standard respectively are divided into different groups through a randomized and blind method. ESAT6-CFP10(10ug/ml) in left arm ESAT6-CFP10(10ug/ml) in right arm. Inject intradermally ESAT6-CFP10 and TB-PPD in different arms of the same participant. For each of participant, the person in this clinical research, the study uniform is that every subject injects firstly left arm, observe no obvious adverse reaction, then another drug inject in right arm. Measure the induration and (or) redness of longitudinal diameter size and transverse diameter vernier caliper by vernier caliper after injection 24h, 48h and 72h. At the same time, we observe the vital signs (breathing, heart rate, blood pressure and temperature), local reactions (rash, pain, itching and skin mucous membrane) and a variety of adverse events. Secondly, 360 cases non-TB participants with lung disease and suspected TB participants are divided into two different groups and the procedure are as the same as 720 cases TB. Thirdly,suspected TB participants are put under TB (Tuberculosis patients) or non-TB participants with lung disease by diagnosis when out group. Finally, we calculate the sensitivity (positive coincidence rate) by TB (Tuberculosis patients), the specificity (negative coincidence rate) by non-TB participants with lung disease, and verify the safety and effectiveness of ESAT6-CFP10(10ug/ml) for the clinical auxiliary diagnosis of tuberculosis.

Official Title
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For Tuberculosis (TB) Clinical Auxiliary Diagnosis of Recombinant Mycobacterium Tuberculosis Allergen ESAT6 - CFP10 Dose of Certain Phase III Clinical Research

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm
* Biological: ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria of TB (tuberculosis:include pulmonary tuberculosis and extra pulmonary tuberculosis) subjects: judge the pulmonary tuberculosis patient according to Health industry standard of the People's Republic of China WS288-2008:Diagnostic Criteria for pulmonary tuberculosis; 18 to 65 years old ,no gender limited; Consent and signed informed consent forms (ICF); Comply with follow-up. Inclusion Criteria of extra pulmonary tuberculosis subjects: Diagnosed extra pulmonary tuberculosis by epidemiology, imaging, clinical symptoms, pathological examination and so on; Lesions outside the lungs; be in unfinished reinforced phase by chemotherapy; Exclusion Criteria of TB (tuberculosis) subjects: Accompanied by the following severe illness:advanced cancer, diabetes, copd in acute episodes, acute/progressive liver disease or kidney disease, congestive heart failure, ect; Taking part in other clinical or within three months involved in any other clinical; Severe allergic constitution:allergic to two or more drugs; in pregnancy or lactation; in a mental illness; Any conditions affect the trial evaluation by investigator's judgement. Inclusion Criteria of non-TB participants with lung disease: A clear lung disease but can exclude pulmonary tuberculosis by clinical symptoms, imaging, laboratory examination. 18 to 65 years old, no gender limited; Consent and signed informed consent forms (ICF); Comply with follow-up. Exclusion Criteria of non-TB participants with lung disease: Accompanied by the following severe illness: advanced cancer, diabetes, copd in acute episodes, acute/progressive liver disease or kidney disease, congestive heart failure, ect; Taking part in other clinical or within three months involved in any other clinical; Severe allergic constitution: allergic to two or more drugs; in pregnancy or lactation; in a mental illness; history of tuberculosis; Any conditions affect the trial evaluation by investigator's judgement. Inclusion Criteria of suspected TB participants with lung disease: Cases who have pulmonary tuberculosis by clinical symptoms/signs:appear cough、cough with hemoptysis、pectoralgia、dyspnea、fever（low-grade fever at afternoon）,together with night sweats、weak、loss of appetite、weight loss,and so on,or other easily-confused respiratory system disease with TB; 18 to 65 years old, no gender limited; Consent and signed informed consent forms (ICF); Comply with follow-up. Exclusion Criteria of suspected TB participants with lung disease: Accompanied by the following severe illness: advanced cancer, diabetes, copd in acute episodes, acute/progressive liver disease or kidney disease, congestive heart failure, ect; Taking part in other clinical or within three months involved in any other clinical; Severe allergic constitution: allergic to two or more drugs; in pregnancy or lactation; in a mental illness; history of tuberculosis; Any conditions affect the trial evaluation by investigator's judgement.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TB subjects<br>720 cases TB (Tuberculosis) subjects who meet the standard respectively are divided average into two groups through a randomized and blind method. 360 TB subjects are injected ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm. 360 TB subjects are injected ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm. For each of participant,the person in this clinical research, the study uniform is that every subject injects firstly left arm, observe no obvious adverse reaction, then another drug inject in right arm. Measure the induration and (or) redness of longitudinal diameter size and transverse diameter vernier caliper by vernier caliper after injection 24h, 48h and 72h. | Biological: ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm<br>* All subjects including TB subjects and non-TB subjects with lung disease inject ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm respectively. Two drug must use at the same participant and in different arms.<br>Biological: ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm<br>* All subjects including TB subjects and non-TB subjects with lung disease inject ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm respectively. Two drug must use at the same participant and in different arms.<br>|
| Experimental: non-TB subjects with lung disease and suspected TB subjects<br>360 cases non-TB subjects with lung disease and suspected TB subjects,who meet the standard respectively are divided average into different groups through a randomized and blind method. 180 non-TB subjects with lung disease are injected ESAT6-CFP10(10ug/ml) in left arm and TB-PPD in right arm. 180 non-TB subjects with lung disease are injected ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm. The study uniform is that every subject injects firstly left arm, observe no obvious adverse reaction, then another drug inject in right arm. Measure the induration and (or) redness of longitudinal diameter size and transverse diameter vernier caliper by vernier caliper after injection 24h, 48h and 72h. | Biological: ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm<br>* All subjects including TB subjects and non-TB subjects with lung disease inject ESAT6-CFP10 (10ug/ml) in left arm and TB-PPD in right arm respectively. Two drug must use at the same participant and in different arms.<br>Biological: ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm<br>* All subjects including TB subjects and non-TB subjects with lung disease inject ESAT6-CFP10 (10ug/ml) in right arm and TB-PPD in left arm respectively. Two drug must use at the same participant and in different arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response of left arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in TB patients | We measure the size of induration or redness at 24h, 48h, 72h after administered intradermally left arm (random injected ESAT6-CFP10 or PPD) | within 72h after injection | 
| Immune response of right arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in TB patients | We measure the size of induration or redness at 24h, 48h, 72h after administered intradermally right arm (random injected ESAT6-CFP10 or PPD) | within 72h after injection | 
| Immune response of left arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in non-TB subjects with lung disease | We measure the size of induration or redness at 24h, 48h, 72h after administered intradermally left arm (random injected ESAT6-CFP10 or PPD) | within 72h after injection | 
| Immune response of right arm (random injected ESAT6-CFP10 or PPD) from the size of induration or redness in non-TB subjects with lung disease | We measure the size of induration or redness at 24h, 48h, 72h after administered intradermally right arm (random injected ESAT6-CFP10 or PPD) | within 72h after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events |  | within 72h after injection two drug each participant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diagnosis of tuberculosis, ESAT6-CFP10, skin test, diagnostic test