Clinical Study of Recombinant Mycobacterium Tuberculosis ESAT6-CFP10 Allergen for Children

Study Overview
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Brief Summary
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In this clinical research,48 cases TB (Tuberculosis patients) participants and 48 cases non-TB participants with lung disease 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 in order to assess the safety of drug.

Detailed Description
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In this clinical research,we make sure of the safety in the crowd 5-18 years old firstly,then carry out the crowd of under 5 years old(including 5). Firstly, 24 cases TB (Tuberculosis) participants and 24 cases non-TB participants with lung disease who are all 5-18 years old and meet the standard respectively are divided into different groups through a randomized and blind method. ESAT6-CFP10(10ug/ml) in left arm and TB-PPD in right arm ESAT6-CFP10(10ug/ml) in right arm and TB-PPD in left 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, 24 cases TB (Tuberculosis) participants and 24 cases non-TB participants with lung disease who are all less than 5 years old are divided into two different groups and the procedure are as the same as 5-18 years old. 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 Certain Phase III Clinical Research in Children Under the Age of 18 Years Old

Conditions
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Tuberculosis Diagnosis

Intervention / Treatment
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* Biological: ESAT6-CFP10 in left arm and TB-PPD in right arm
* Biological: ESAT6-CFP10 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 Chinese Medical Association branch of pediatrics breathing group: Tuberculosis Clinical Diagnostic Criteria and Treatment Programs for Child (trial) ; less than 18 years old ,no gender limited; Consent and signed informed consent forms (ICF) by the subject or the guardian; The subject or with the help of guardian(s) 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: cancer, acute/progressive liver disease or kidney disease,autoimmune disease，diabetes, primary immunodeficiency diseases, other chronic diseases; Taking part in other clinical or within three months involved in any other clinical; Severe allergic constitution or familial history of allergy: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 respiratory disease but can exclude pulmonary tuberculosis by clinical symptoms, imaging, laboratory examination. less than 18 years old ,no gender limited; Consent and signed informed consent forms (ICF) by the subject or the guardian; The subject or with the help of guardian(s) comply with follow-up. Exclusion Criteria of non-TB participants with lung disease: Accompanied by the following severe illness: cancer, acute/progressive liver disease or kidney disease,autoimmune disease，diabetes, primary immunodeficiency diseases, other chronic diseases， ect; Taking part in other clinical or within three months involved in any other clinical; Severe allergic constitution or familial history of allergy: allergic to two or more drugs; in pregnancy or lactation; in a mental illness; active tuberculosis close contactor; Any conditions affect the trial evaluation by investigator's judgement.

Ages Eligible for Study
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Maximum Age: 17 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 in 5-18 years old<br>24 cases TB subjects in 5-18 years old are injected ESAT6-CFP10 in left arm and TB-PPD in right arm or ESAT6-CFP10 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 in left arm and TB-PPD in right arm<br>* All subjects including TB subjects in 5-18 years old、non-TB subjects in 5-18 years old、TB subjects under 5 years old and non-TB subjects under 5 years old inject ESAT6-CFP10 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 in right arm and TB-PPD in left arm<br>* All subjects including TB subjects in 5-18 years old、non-TB subjects in 5-18 years old、TB subjects under 5 years old and non-TB subjects under 5 years old inject ESAT6-CFP10 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 in 5-18 years old<br>24 cases non-TB subjects in 5-18 years old are injected ESAT6-CFP10 in left arm and TB-PPD in right arm or ESAT6-CFP10 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 in left arm and TB-PPD in right arm<br>* All subjects including TB subjects in 5-18 years old、non-TB subjects in 5-18 years old、TB subjects under 5 years old and non-TB subjects under 5 years old inject ESAT6-CFP10 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 in right arm and TB-PPD in left arm<br>* All subjects including TB subjects in 5-18 years old、non-TB subjects in 5-18 years old、TB subjects under 5 years old and non-TB subjects under 5 years old inject ESAT6-CFP10 in right arm and TB-PPD in left arm respectively. Two drug must use at the same participant and in different arms.<br>|
| Experimental: TB subjects under 5 years old<br>24 cases TB subjects under 5 years old are injected ESAT6-CFP10 in left arm and TB-PPD in right arm or ESAT6-CFP10 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 in left arm and TB-PPD in right arm<br>* All subjects including TB subjects in 5-18 years old、non-TB subjects in 5-18 years old、TB subjects under 5 years old and non-TB subjects under 5 years old inject ESAT6-CFP10 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 in right arm and TB-PPD in left arm<br>* All subjects including TB subjects in 5-18 years old、non-TB subjects in 5-18 years old、TB subjects under 5 years old and non-TB subjects under 5 years old inject ESAT6-CFP10 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 under 5 years old<br>24 cases non-TB subjects under 5 years old are injected ESAT6-CFP10 in left arm and TB-PPD in right arm or ESAT6-CFP10 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 in left arm and TB-PPD in right arm<br>* All subjects including TB subjects in 5-18 years old、non-TB subjects in 5-18 years old、TB subjects under 5 years old and non-TB subjects under 5 years old inject ESAT6-CFP10 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 in right arm and TB-PPD in left arm<br>* All subjects including TB subjects in 5-18 years old、non-TB subjects in 5-18 years old、TB subjects under 5 years old and non-TB subjects under 5 years old inject ESAT6-CFP10 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 |
| --- | --- | --- |
| The diameter of induration or redness at the injection sites measured transversely to the long axis of the forearm 24 hours、48 hours and 72 hours after application of the agents | After skin test 1-3d,subjects's injection site may appear inuration or redness .The diameters of induration or redness are measured and recorded.The number of diameter of induration or redness<5mm，the result is negtive.If the number of diameter are not lower than 5mm,the result is positive. | From injections to 1-3 days after aplication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events | Any AE of every subject appeared is recorded and traced after signing ICF,until remission of AE. | 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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diagnostic test, children, diagnosis of tuberculosis