Clinical trial NCT04150367: Efficacy and Safety of Intravenous Treatment of Tuberculosis
Official title: Open-label, Randomized, Multicenter, Controlled, Parallel, Comparative Study of Efficacy and Safety of Treatment of Tuberculosis With Isoniazid, Rifampicin, Ethambutol for Intravenous Infusion in Comparison With Oral Forms While the Intensive Phase of Treatment for Patients With Widespread Destructive Pulmonary Tuberculosis With Bacterial Excretion.
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Tuberculosis, Pulmonary
Lead sponsor: Yuria-Pharm
Sponsor class: INDUSTRY
First posted: 2019-11-04
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with first diagnosed widespread destructive pulmonary tuberculosis with bacterial excretion.

Brief summary: This Open-label, Randomized, Multicenter, Controlled, Parallel, Comparative Study will compare the efficacy and safety of intravenous treatment with Isoniazid, Rifampicin, Ethambutol first two months of intensive phase of tuberculosis treatment and the treatment with the oral forms of Isoniazid, Rifampicin, Ethambutol first two months of intensive phase of tuberculosis treatment for Patients With Widespread Destructive Pulmonary Tuberculosis With Bacterial Excretion.

Detailed description: There are two groups of patients with first diagnosed widespread destructive pulmonary tuberculosis with bacterial excretion. The first group receives intravenous treatment with Isoniazid, Rifampicin, Ethambutol first two months of intensive phase of tuberculosis treatment. The second group gets oral forms of Isoniazid, Rifampicin, Ethambutol first two months of intensive phase of Tuberculosis treatment. Then both groups receive oral treatment of tuberculosis according to the known scheme.

Up to 318 participants will be randomized into this study, with 159 participants being randomized to the control arm and 159 participants being randomized to the experimental arm. It Supposed that not less than 254 participants will finish the study (about 127 participants in each arm) and their results will be included in the statistical analysis.

While the intensive phase participants of both arms will be hospitalized in the Tuberculosis Dispensary.

Eligibility criteria: Inclusion Criteria:

1. men and women;
2. The age of 18 - 65 years inclusive;
3. Patients diagnosed with: first diagnosed pulmonary tuberculosis;
4. Patients with at least one positive result of a microbiological study of the sputum on the Mycobacterium tuberculosis (during the screening, the results of a microbiological sputum examination on an Mycobacterium tuberculosis up to 7 days old can be used);
5. Patients with radiographically and optionally CT confirmed cavity / cavities of destruction in the lungs, as well as a widespread tuberculosis process (occupying at least 2 segments of the lungs) (during the screening, the results of X-ray examination of the chest up to 7 days old can be used );
6. For women with reproductive potential - negative result of urine test for pregnancy and consent to use a reliable method of contraception before the end of the study;
7. Provided informed written consent of the patient to participate in the study;
8. The patient's ability to adequately cooperate in the research process;
9. Patients with negative analysis of GenXpert MBT / RIF (at the time of screening, analysis results not older than 7 days may be used);
10. Oral consent of the patient to stop using alcohol during the study period.

Exclusion Criteria:

1. Patients who, according to the results of a sputum test using the GenXpert MBT / RIF method, are determined to be resistant to rifampicin.
2. Pregnancy, lactation;
3. Epilepsy and other diseases, which are accompanied by a tendency to convulsive seizures;
4. Severe psychosis;
5. Poliomyelitis (including in the anamnesis);
6. Diseases of the cardiovascular system, respiratory system, diabetes mellitus, impaired liver function, kidney, thyroid gland, vision, the presence of concomitant diseases or acute conditions, which, according to the researcher, do not allow the patient to participate in this study;
7. HIV infection;
8. Intolerance (including history) of any of the drugs studied;
9. Participation in any other clinical trial at the time of inclusion in this study and for the last 30 days before the date of screening.

Primary outcomes:
measure: Percentage of patients with negative results of sputum analysis on Mycobacterium tuberculosis .
timeFrame: Тhe end of the 1st month from the start of treatment (after taking 30 doses of each drug by the patient)
Secondary outcomes:
measure: Time until the negative result of the Mycobacterium tuberculosis tests is obtained.
timeFrame: 2 weeks - 3 months
measure: Combined percentage ratio of patients with negative results of Mycobacterium tuberculosis analysis and clinical improvement.
timeFrame: 2 months after the start of treatment (after taking the patient 60 doses of each preparation of the intensive phase).
measure: Combined percentage of patients with no response to treatment in 12 months.
timeFrame: 12 months after the start of treatment (13 months after initiation of treatment for patients who still have the positive results of the sputum analysis on Mycobacterium tuberculosis after taking 60 doses of each preparation of the intensive phase).
measure: Combined percentage ratio of patients with no response to treatment in 18 months.
timeFrame: 18 months after the start of treatment (19 months after initiation of treatment for patients who still have the positive results of the sputum analysis on Mycobacterium tuberculosis after taking 60 doses of each preparation of the intensive phase).
measure: Combined percentage ratio of patients with relapse of active tuberculosis in 18 months.
timeFrame: 18 months after the start of treatment (19 months after initiation of treatment for patients who still have the positive results of the sputum analysis on Mycobacterium tuberculosis after taking 60 doses of each preparation of the intensive phase).
measure: Combined percentage ratio of patients with death due to active tuberculosis in 18 months.
timeFrame: 18 months after the start of treatment (19 months after initiation of treatment for patients who still have the positive results of the sputum analysis on Mycobacterium tuberculosis after taking 60 doses of each preparation of the intensive phase).
measure: Combined percentage ratio of patients with relapse of active tuberculosis in 12 months.
timeFrame: 12 months after the start of treatment (13 months after initiation of treatment for patients who still have the positive results of the sputum analysis on Mycobacterium tuberculosis after taking 60 doses of each preparation of the intensive phase).
measure: Combined percentage ratio of patients with death due to active tuberculosis in 12 months.
timeFrame: 12 months after the start of treatment (13 months after initiation of treatment for patients who still have the positive results of the sputum analysis on Mycobacterium tuberculosis after taking 60 doses of each preparation of the intensive phase).
Other outcomes:
measure: Percentage ratio of severe adverse events.
timeFrame: From 1 week till 7 months after the start of treatment.
measure: Comparative cost of treatment of the main disease and complications at 6 months after the start of the treatment.
timeFrame: 6 months after the start of treatment/
measure: Comparative cost of treatment of the main disease and complications at 12 months after the start of the treatment.
timeFrame: 12 months after the start of treatment
measure: Comparative cost of treatment of the main disease and complications at 18 months after the start of the treatment.
timeFrame: 18 months after the start of treatment
Locations:
city: Chernivtsi
country: Ukraine
facility: Regional Clinical Antituberculosis Dispensary
city: Ivano-Frankivs'k
country: Ukraine
facility: Regional phthisiopulmonary center
city: Kharkiv
country: Ukraine
facility: Regional Antituberculosis Dispensary №1
city: Kherson
country: Ukraine
facility: Regional Antituberculosis Dispensary
city: Kyiv
country: Ukraine
facility: National Yanovsky's Institute of Phthisiology and Pulmonology
city: L'viv
country: Ukraine
facility: Lviv Regional Phthisiopneumological Clinical Treatment and Diagnostic Center
city: Luts'k
country: Ukraine
facility: Regional territorial medical anti-tuberculosis association
city: Sumy
country: Ukraine
facility: Regional Clinical Antituberculosis Dispensary
city: Ternopil'
country: Ukraine
facility: Ternopil Regional TB Dispensary
Study officials:
References: