Efficacy and Safety of Intravenous Treatment of Tuberculosis

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.

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.

Study Overview

• Status: Terminated
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: Isoniazid; Drug: Rifampicin; Drug: Ethambutol; Drug: Isoniazid

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.

• Study Type: Observational
• Enrollment (Actual): 166

Contacts and Locations

Study Locations

• Ukraine
  • Chernivtsi, Ukraine
    • Regional Clinical Antituberculosis Dispensary
  • Ivano-Frankivs'k, Ukraine
    • Regional phthisiopulmonary center
  • Kharkiv, Ukraine
    • Regional Antituberculosis Dispensary №1
  • Kherson, Ukraine
    • Regional Antituberculosis Dispensary
  • Kyiv, Ukraine
    • National Yanovsky's Institute of Phthisiology and Pulmonology
  • L'viv, Ukraine
    • Lviv Regional Phthisiopneumological Clinical Treatment and Diagnostic Center
  • Luts'k, Ukraine
    • Regional territorial medical anti-tuberculosis association
  • Sumy, Ukraine
    • Regional Clinical Antituberculosis Dispensary
  • Ternopil', Ukraine
    • Ternopil Regional TB Dispensary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with first diagnosed widespread destructive pulmonary tuberculosis with bacterial excretion.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Patients with first diagnosed widespread destructive pulmonary tuberculosis with bacterial excretion, who receive intravenous treatment with Isoniazid, Rifampicin, Ethambutol first two months of intensive phase of tuberculosis treatment. Then group receives oral treatment of tuberculosis according to the known scheme.	Drug: Isoniazid; Solution for injections, 100 mg/ml, 5 ml. Participants will get the dosage according to the instruction for use.; Other Names: Bitub; Drug: Rifampicin; Participants will get the dosage according to the instruction for use.; Other Names: Rifampicin 150 mg Capsules; Drug: Ethambutol; Participants will get the dosage according to the instruction for use.; Other Names: Ethambutol, Tablets 400 mg.; Drug: Isoniazid; . Participants will get the dosage according to the instruction for use.; Other Names: Isoniazid, Tablets, 300mg.
Control group; Patients with first diagnosed widespread destructive pulmonary tuberculosis with bacterial excretion, who receive oral forms of Isoniazid, Rifampicin, Ethambutol first two months of intensive phase of tuberculosis treatment. Then group receives oral treatment of tuberculosis according to the known scheme.	Drug: Isoniazid; Solution for injections, 100 mg/ml, 5 ml. Participants will get the dosage according to the instruction for use.; Other Names: Bitub; Drug: Rifampicin; Participants will get the dosage according to the instruction for use.; Other Names: Rifampicin 150 mg Capsules; Drug: Ethambutol; Participants will get the dosage according to the instruction for use.; Other Names: Ethambutol, Tablets 400 mg.; Drug: Isoniazid; . Participants will get the dosage according to the instruction for use.; Other Names: Isoniazid, Tablets, 300mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with negative results of sputum analysis on Mycobacterium tuberculosis .	Percentage of patients with negative results of sputum analysis on Mycobacterium tuberculosis in the main and control groups.	Тhe end of the 1st month from the start of treatment (after taking 30 doses of each drug by the patient)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time until the negative result of the Mycobacterium tuberculosis tests is obtained.	Time until the negative result of sputum Mycobacterium tuberculosis tests is obtained for each patient.	2 weeks - 3 months
Combined percentage ratio of patients with negative results of Mycobacterium tuberculosis analysis and clinical improvement.	Combined percentage ratio of patients who have negative results of sputum analysis on Mycobacterium tuberculosis and clinical improvement at the same time.	2 months after the start of treatment (after taking the patient 60 doses of each preparation of the intensive phase).
Combined percentage of patients with no response to treatment in 12 months.	Combined percentage ratio of patients with no response to treatment in 12 months.	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).
Combined percentage ratio of patients with no response to treatment in 18 months.	Combined percentage ratio of patients with no response to treatment in 18 months.	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).
Combined percentage ratio of patients with relapse of active tuberculosis in 18 months.	Combined percentage ratio of patients with relapse of active tuberculosis in 18 months.	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).
Combined percentage ratio of patients with death due to active tuberculosis in 18 months.	Combined percentage ratio of patients with death due to active tuberculosis in 18 months.	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).
Combined percentage ratio of patients with relapse of active tuberculosis in 12 months.	Combined percentage ratio of patients with relapse of active tuberculosis in 12 months.	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).
Combined percentage ratio of patients with death due to active tuberculosis in 12 months.	Combined percentage ratio of patients with death due to active tuberculosis in 12 months.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage ratio of severe adverse events.	All kinds of adverse events.	From 1 week till 7 months after the start of treatment.
Comparative cost of treatment of the main disease and complications at 6 months after the start of the treatment.	Comparative cost of treatment of the main disease and complications based on the average cost of all medical services for the medical institutions participating in the study at 6 months after the start of treatment.	6 months after the start of treatment/
Comparative cost of treatment of the main disease and complications at 12 months after the start of the treatment.	Comparative cost of treatment of the main disease and complications based on the average cost of all medical services for the medical institutions participating in the study at 12 months after the start of treatment.	12 months after the start of treatment
Comparative cost of treatment of the main disease and complications at 18 months after the start of the treatment.	Comparative cost of treatment of the main disease and complications based on the average cost of all medical services for the medical institutions participating in the study at 18 months after the start of treatment.	18 months after the start of treatment

Collaborators and Investigators

• Sponsor: Yuria-Pharm

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 3, 2017
• Primary Completion (ACTUAL): July 14, 2018
• Study Completion (ACTUAL): July 14, 2018

Study Registration Dates

• First Submitted: October 25, 2017
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (ACTUAL): November 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Fatty Acid Synthesis Inhibitors; Pharmaceutical Solutions; Rifampin; Isoniazid; Ethambutol
• Other Study ID Numbers: Invent-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No