Tuberculosis, MDR
Conditions
Keywords
Tuberculosis, Multi-drug resistant TB, TB treatment
Brief summary
Drug-resistant tuberculosis is becoming a major problem for the whole humanity, and development of new Anti-TB drugs is of great importance. Since Kazakhstan is a country with the high burden of tuberculosis, the Government of the Republic of Kazakhstan has founded initiative on the development of new Anti-TB drug to treat drug-resistant forms of this infectious disease. JSC Scientific Center for Anti-infectious Drugs has developed original drug FS-1 for the treatment of multidrug resistant tuberculosis (MDR-TB).
Detailed description
Phase 3 clinical study of FS-1 drug is a randomized, interventional, multicenter, placebo-controlled (add-on), double-blind and two arms trial. The study consists of two following phases: treatment phase - 6 months and follow-up phase 12 months. It is planned to recruit 480 patients with verified MDR-TB diagnosis. All data will be compiled in an Electronic Data Capture System with further statistical analysis according to approved Statistical Analytical Plan.
Interventions
DRUGFS-1
FS-1 is a liquid solution for internal intake and has antimicrobial and antibacterial activities.
DRUGPlacebo
Placebo without any active pharmaceutical ingredients
Sponsors
Phthisiopulmonology Center of Almaty, Kazakhstan
National Scientific Center of Phthisiopulmonology, Kazakhstan
Karaganda Medical University
West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
Semey State Medical University
National Center of Phthisiatry, Bishkek, Kyrgyzstan
Invivo laboratory, Kazakhstan
Scientific Center for Anti-infectious Drugs, Kazakhstan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects suffering from a multidrug-resistant form of pulmonary tuberculosis which is defined by: * MDR Tuberculosis confirmed by microbiology test at screening. * resistance to isoniazid and rifampicin demonstrated by drug susceptibility test * susceptiblity of TB bacteria to fluoroquinolones and aminoglycoside/capreomycin * all ethnicities, intellectually capable of understanding their own condition and the requirements of the study protocol * Willing to freely and voluntarily give signed informed consent * Willing and capable to comply with all requirements of the protocol
Exclusion criteria
* Pregnancy and breast-feeding; * Patients with decompensated concomitant diseases (cardiovascular, renal, hepatic failure) that may affect the conduct of the study; * Severe mental disorders; * Allergy to iodine-containing drugs, hypersensitivity to iodine; * Intolerance to second-line drugs; * Epidermomycosis * Socially maladjusted patients suffering from alcoholism and drug addiction; * Hypothyroidism; * Hashimoto's thyroiditis; * TB treatment for more than two months before the start of the study; * Not willing to adhere to TB therapy;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to persistently negative sputum cultures | 18 months | Time from the start of treatment with study drug to the first negative M. tuberculosis sputum culture on solid medium followed by 4 consecutive negative results with an interval of at least 30 days. Measured in months. Estimated population: randomized subjects who took at least 70% of planned study drug doses; having a positive bacterial culture M. tuberculosis at the baseline; who missed less than 2 consecutive visits or less than 14 consecutive days of study drug treatment (modified ITT analysis). |
| Proportion of Patients with persistently negative sputum cultures (SCC) | 12 months | Sputum culture conversion (SCC) is a persistently negative result of the sputum culture at one year from the patients who had sputum samples positive for growth of M. tuberculosis at baseline and not followed by any positive culture until the end of the trial. SCC corresponds to the outcome cured if at least 5 negative bacteriological cultures is recorded (on solid medium) during 12 months with an interval of at least 30 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The median time to occurrence of negative sputum microscopy result | 18 months | The average time between positive and negative sputum smear microscopy results during the treatment. |
| The time when TB clinical symptoms not observed | 18 months | Assessment of period between TB clinical symptoms and their disappearance. Observed of TB clinical symptoms are as follows: chest pain, difficulties to breath, cough, sputum, intoxication symptoms. |
| The proportion of subjects with relapse of tuberculosis | 12 months | Relapse is defined when patient received full study drug treatment course (6 months) and bacteriological culture become again positive after 5 negative bacteriological cultures (on solid medium) during 12 months with an interval of at least 30 days. |
| The incidence and severity of Adverse Events, Serious Adverse Events and drug related Adverse Drug Reactions | 18 months | Assessment of Adverse Events and Drug Reactions during the study (6 months of treatment and 12 months of follow-up period). Adverse event (AE) is any untoward medical occurrence in subject administered the study drug and that does not necessarily have a causal relationship with this treatment. AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not related to the study drug. Serious Adverse Event is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect. Adverse drug reaction - all noxious and unintended responses to the study drug, when a causal relationship between the study drug and an adverse event is at least a reasonable possibility. |
| Assessment of the study drug effect on thyroid gland function | 18 months | Assessment of thyroid hormones and antibodies in the blood (free triiodothyronine (FT3), free thyroxine (FT4), total thyroxine (TT4),total triiodothyronine (TT3),thyroid stimulating hormone (TSH), antibodies to thyroglobulin and thyroid peroxidase), and results of ultrasound of the thyroid gland before treatment, during treatment (6 months) and during the follow-up period (12 months). |
| Dynamics of the tuberculosis process based on subjects chest x-ray diagnosis. | 18 months | The positive dynamics of the subject X-ray picture of the tuberculous process is characterized by the closure of TB caused cavities, a decrease of lung infiltration, nodular lesions, pleural effusion and lymphadenopathy. |
| Patients body weight dynamics for the period of 18 months. | 18 months | Comparison of subjects' weight, using as the baseline subjects' weight before the start of the treatment with the subjects' weight during the treatment cycle with the study drug (6 months) and during 12 months of follow-up period. |
Countries
Kazakhstan, Kyrgyzstan
Outcome results
None listed