Study on the Use of Interferon Gamma (Ingaron) Injections in Patients With Drug-resistant Pulmonary Tuberculosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and tolerability of the complex therapy of drug-resistant respiratory tuberculosis using the drug Ingaron, a lyophilisate for the preparation of a solution for injection for intramuscular or subcutaneous administration of 500,000 IU.

Detailed Description
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Open prospective observational cohort study. During the recruitment phase, a preliminary assessment of eligibility and non-inclusion criteria will be carried out. Subject to prior compliance with all inclusion criteria and none of the exclusion criteria, after signing a voluntary informed consent, the patient will be included in the study. Patients will be divided into groups, depending on the therapy prescribed to them as part of routine clinical practice (according to clinical guidelines): Group 1: Pathogenetic therapy with the use of the drug Ingaron + basic anti-tuberculosis therapy in accordance with approved clinical guidelines. Group 2: Basic anti-tuberculosis therapy in accordance with approved clinical guidelines. When a patient is included in the study (Visit 0), an initial examination will be carried out, in accordance with generally accepted principles of treatment monitoring, which includes: history taking, physical examination, registration of vital signs, ECG, blood samples for general clinical, biochemical analysis, general analysis urine, bacteriological examination by sputum smear microscopy and sputum culture on dense nutrient media with drug sensitivity assessment, computed tomography and chest radiography. The inclusion/exclusion criteria will be checked. The expected duration of the study for each patient will be no more than 204 days. After the start of therapy, patients will be recorded monthly with physical examination data with registration of vital signs, general clinical, biochemical analyzes, urinalysis, smear microscopy and sputum culture. X-ray examination and clinical evaluation of effectiveness will be carried out every 2 months. At visit 7 (after 6 months from the start of therapy), an evaluation of computed tomography and chest x-ray in dynamics with an assessment of the effectiveness of therapy, as well as ECG, physical examination with registration of vital signs, general clinical, biochemical analyzes, general urinalysis, smear microscopy and culture of sputum. At visits 1, 4 and 7 immunological parameters will be assessed.

Official Title
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An Open Prospective Observational Study Evaluating the Efficacy and Tolerability of Interferon Gamma (Ingaron) Injections in Patients With Drug-resistant Pulmonary Tuberculosis

Conditions
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Pulmonary Tuberculosis

Intervention / Treatment
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* Drug: Interferon-Gamma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or non-pregnant women 18-75 years of age. For women of childbearing age who are fertile: Agree to completely abstain from sexual intercourse or use dual methods of contraception to prevent pregnancy while participating in the study. Verified diagnosis of pulmonary tuberculosis (infiltrative tuberculosis, fibrous-cavernous tuberculosis in the infiltration phase). A positive sputum smear microscopy test result for acid-fast bacterium, assessed as moderate (++) or massive bacterial excretion (+++) no earlier than 30 days prior to enrollment in the study. Established resistance of the isolated pathogen to at least rifampicin, determined by molecular genetic or cultural methods for determining drug susceptibility. Prescribing the current baseline chemotherapy regimen according to clinical guidelines no earlier than 14 days prior to enrollment in the study. Compliance with prescribed therapy. No concomitant immunotherapy, or 6 months from the last dose of an immunomodulatory drug to the start of therapy. Absence of comorbidities and therapy that may affect the interpretation of study results, in the opinion of the investigator. Signed written informed consent to participate in the study. Willingness and ability to follow protocol requirements throughout the study. Exclusion Criteria: For women: pregnant, breastfeeding or planning a pregnancy during the study period. Caseous pneumonia. Asthma, with the exception of mild intermittent asthma. Systemic fungal infections. Use of any investigational drug within 30 days prior to screening. Oncological diseases (cytotoxic chemotherapy, current or received within the last 3 months before the start of treatment). Chronic diseases of the liver or kidneys (an increase in liver transaminases more than 5 times the upper limit of laboratory norms for these indicators; an increase in creatinine above 2 mg / 100 ml (or μmol / l)). Diabetes. HIV infection or other immunodeficiency conditions. Inability, in the opinion of the investigator, to comply with the treatment regimen and the requirements of the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental<br>Ingaron + basic TB therapy 500,000 IU once daily for 3 months followed by 3 months follow-up | Drug: Interferon-Gamma<br>* received by microbiological synthesis; specific antiviral activity on cells is 2x10*7 Units per mg of protein<br>* Other names: Interferon gamma human recombinant;|
| No Intervention<br>only basic anti-tuberculosis therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Percentage of patients. | 1 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Mean time to clinical response. | 1 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Percentage of patients. | 2 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Mean time to clinical response. | 2 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Percentage of patients. | 3 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Mean time to clinical response. | 3 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Percentage of patients. | 4 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Mean time to clinical response. | 4 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Percentage of patients. | 5 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Mean time to clinical response. | 5 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Percentage of patients. | 6 months | 
| Sputum smear conversion according to microscopy. | Sputum smear conversion according to microscopy. Mean time to clinical response. | 6 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Percentage of patients. | 1 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Mean time to clinical response. | 1 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Percentage of patients. | 2 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Mean time to clinical response. | 2 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Percentage of patients. | 3 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Mean time to clinical response. | 3 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Percentage of patients. | 4 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Mean time to clinical response. | 4 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Percentage of patients. | 5 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Mean time to clinical response. | 5 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Percentage of patients. | 6 months | 
| Sputum smear conversion by culture. | Sputum smear conversion by culture. Mean time to clinical response. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effectiveness of therapy according to X-ray examination of the chest. | The effectiveness of therapy according to X-ray examination of the chest. Percentage of patients. | 2 months | 
| The effectiveness of therapy according to X-ray examination of the chest. | The effectiveness of therapy according to X-ray examination of the chest. Percentage of patients. | 4 months | 
| The effectiveness of therapy according to X-ray examination of the chest. | The effectiveness of therapy according to X-ray examination of the chest. Percentage of patients. | 6 months | 
| The effectiveness of therapy according to computed tomography of the chest. | The effectiveness of therapy according to computed tomography of the chest. Percentage of patients. | 6 months | 
| The effectiveness of therapy according to clinical examination. | The effectiveness of therapy according to clinical examination. Average score. The dynamics of clinical symptoms will be determined based on an assessment of the severity of intoxication (general) symptoms and respiratory complaints according to a 4-point system, where the minimum score is 0 - absent, the maximum 3 - pronounced | 2 months | 
| The effectiveness of therapy according to clinical examination. | The effectiveness of therapy according to clinical examination. Average score. The dynamics of clinical symptoms will be determined based on an assessment of the severity of intoxication (general) symptoms and respiratory complaints according to a 4-point system, where the minimum score is 0 - absent, the maximum 3 - pronounced | 4 months | 
| The effectiveness of therapy according to clinical examination. | The effectiveness of therapy according to clinical examination. Average score. The dynamics of clinical symptoms will be determined based on an assessment of the severity of intoxication (general) symptoms and respiratory complaints according to a 4-point system, where the minimum score is 0 - absent, the maximum 3 - pronounced | 6 months | 
| Change in immunological status (CD4 and CD8 lymphocyte populations) compared with baseline values (before therapy). | Change in immunological status (CD4 and CD8 lymphocyte populations) compared with baseline values (before therapy). Averages. | 3 months | 
| Change in immunological status (CD4 and CD8 lymphocyte populations) compared with baseline values (before therapy). | Change in immunological status (CD4 and CD8 lymphocyte populations) compared with baseline values (before therapy). Averages. | 6 months | 
| Mortality rate. | Mortality rate. The proportion of patients. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment of drug-resistant pulmonary tuberculosis, interferon gamma, drug resistant