- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05047055
Four Months Moxifloxacin Containing Daily Regimen Study Among New Pulmonary Tuberculosis Patients
Multi-centric Prospective Cohort Study of TB Recurrence Free Cure Among Microbiologically Confirmed New Pulmonary Tuberculosis Patients Treated Under NTEP With the 4-month Moxifloxacin Containing Daily Regimen
The 4-month daily regimen containing moxifloxacin (2HRZEM 7 / 2HRM7) of ICMR-NIRT was studied in 321 sputum positive pulmonary TB patients in a randomised clinical trial. Of the 321, there were 96% with sputum smear grading of 2+/3+ and 80% with >2 zone involvement in the chest radiograph, The sputum culture conversion at the end of intensive phase was 94%, favourable response at the end of treatment of 92% and the TB recurrence rate was 4.1%. The regimen was safe and well tolerated.
The advantages of a 33% reduction in treatment duration are manifold in terms of financial and other administrative implications. As the next logical step investigators believe that the effectiveness of this shortened regimen that proved successful in our study needs to be tested in the field. Under NTEP the anti-TB drugs are offered as Fixed dose Combination (FDC).3 The HREZ intensive phase and HRE continuation phase FDC are administered to patients based on body weight category. If our proposed study proves successful, the addition of moxifloxacin tablet to the FDC of anti-TB drugs in the intensive and continuation phases of treatment would be feasible under TB program settings. Investigators propose to evaluate 4-month moxifloxacin containing daily regimen [2 months of HRZEM daily / 2 months of HREM daily (2 HRZEM 7 / 2HREM7)] in the treatment of newly diagnosed sputum smear positive pulmonary TB patients.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Scientific rationale The 4-month daily regimen containing moxifloxacin (2HRZEM 7 / 2HRM7) of ICMR-NIRT was studied in 321 sputum positive pulmonary TB patients in a randomised clinical trial.7 Of the 321, there were 96% with sputum smear grading of 2+/3+ and 80% with >2 zone involvement in the chest radiograph, The sputum culture conversion at the end of intensive phase was 94%, favourable response at the end of treatment of 92% and the TB recurrence rate was 4.1%. The regimen was safe and well tolerated.
The advantages of a 33% reduction in treatment duration are manifold in terms of financial and other administrative implications. As the next logical step investigators believe that the effectiveness of this shortened regimen that proved successful in our study needs to be tested in the field. Under NTEP the anti-TB drugs are offered as Fixed dose Combination (FDC). The HREZ intensive phase and HRE continuation phase FDC are administered to patients based on body weight category. If our proposed study proves successful, the addition of moxifloxacin tablet to the FDC of anti-TB drugs in the intensive and continuation phases of treatment would be feasible under TB program settings. Investigators propose to evaluate 4-month moxifloxacin containing daily regimen [2 months of HRZEM daily / 2 months of HREM daily (2 HRZEM 7 / 2HREM7)] in the treatment of newly diagnosed sputum smear positive pulmonary TB patients.
Objectives :
Primary objective:
To determine the TB recurrence free cure rate among microbiologically confirmed new pulmonary tuberculosis (PTB) patients treated under NTEP with the 4-month moxifloxacin containing daily regimen.
Secondary objectives:
- To determine the Adverse drug reactions (ADR) with the 4-month moxifloxacin containing daily regimen
- To determine to response to treatment with the 4-month moxifloxacin containing daily regimen
- To store paired samples of culture isolates of patients with TB recurrence for future genotyping.
Study sites: Nagpur, Lucknow, Delhi, Hyderabad, Vellore (5 sites) Study population: Newly diagnosed adult sputum smear and or CBNAAT positive PTB patients
Sample size calculated was 550 patients.
Screening assessments Clinical evaluation, Laboratory evaluations will be done initially.
Positive sputum isolates at baseline and at the time of TB recurrence will be sent to ICMR-NIRT, Chennai for storage for future genotyping.
Follow-up Follow-up during treatment: During the treatment phase the patients will be followed every month
Follow-up post- treatment :
During post-treatment, the patients will be followed up once in 3 months at 3, 6, 9 and 12 months and once every six months upto 24 months (ie. at 18 and 24 months). The 95% confidence interval of the TB recurrence free cure rate will be used to conclude on the performance of the 4 month moxifloxacin containing regimen under program settings.
Study duration:
Recruitment, training of staff: 2 month Duration of enrollment : 10 months Duration of treatment: 4 months Follow-up period : 24 months post-treatment Data analysis and report generation : 2 months Total study duration: 3.5 years
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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-
Tamilnadu
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Chennai, Tamilnadu, India, 600031
- National Institute for Research in Tuberculosis
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Age 18 to 65 years
- At least one sputum smear and or CBNAAT test should be positive for tubercle bacilli
- Female participants of childbearing potential must have a negative urine pregnancy test at screening. Those who have not undergone permanent sterilisation - tubal ligation or spouse with vasectomy must agree for use of contraceptive measures for birth control - vaginal diaphragm, intrauterine device, condom until treatment completion.
- Willing to follow the trial procedures
- Willing to give written informed consent
- Residing within the study TU
Exclusion Criteria:
- Body weight less than 30 kg
- Previous anti-TB treatment, if any, should not exceed one month in the past 2 years and more than 7 days in the preceding one month
- Multidrug resistant TB (MDR-TB)
- Resistance to isoniazid or rifampicin or quinolone as evidenced by Cartridge based Nucleic acid Amplification test (CBNAAT) and Line probe Assay (LPA) test
- Associated extra-pulmonary TB except TB superficial lymphadenitis
- Hepatic or renal disease as evidenced by clinical or biochemical abnormalities- ALT/AST> 2.5 times ULN or Total bilirubin >1.2 mg/dl, Serum Creatinine >1.2 mg/dl, Blood Urea >43 mg/dl.
- QTcF> 450 ms or bundle branch block or heart block on ECG
- Psychiatric illness
- Seizure disorder
- Pregnancy or lactation
- Those seriously ill as defined by a score of <50 on Karnofsky scale (Annexure 1)
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Single Group - 4 months moxifloxacin group
Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E), Moxifloxacin (M) Isoniazid, rifampicin, pyrazinamide, ethambutol and moxifloxacin daily for 2 months followed by isoniazid, rifampicin, ethambutol and moxifloxacin daily for 2 months (2 HRZEM daily / 2HREM daily) - Duration 4 months Drug dosages The Fixed-dose Combination (FDC) for HRZE(75/150/400/275mg) used under NTEP according to weight category will be used. The patients enrolled in the study will receive an additional tablet of moxifloxacin(M) 400mg (body weight <64 Kg) / 600mg (body weight >65 Kg) along with the FDC both in the intensive and continuation phase. |
Intensive Phase for 2 months and Continuation phase for 2 months dose: 75 mg (2 tablets for 30 - 34 Kg, 3 tablets for 35 - 49 Kg, 4 tablets for 50 - 64 Kg, 5 tablets for 65 - 75 Kg and 6 tablets for >75 Kg) as a fixed-dose combination.
Other Names:
Intensive Phase for 2 months and Continuation phase for 2 months dose: 150 mg (2 tablets for 30 - 34 Kg, 3 tablets for 35 - 49 Kg, 4 tablets for 50 - 64 Kg, 5 tablets for 65 - 75 Kg and 6 tablets for >75 Kg) as a fixed-dose combination.
Other Names:
Intensive Phase for 2 months only dose: 400 mg (2 tablets for 30 - 34 Kg, 3 tablets for 35 - 49 Kg, 4 tablets for 50 - 64 Kg, 5 tablets for 65 - 75 Kg and 6 tablets for >75 Kg) as a fixed-dose combination.
Other Names:
Intensive Phase for 2 months and Continuation phase for 2 months dose: 275 mg (2 tablets for 30 - 34 Kg, 3 tablets for 35 - 49 Kg, 4 tablets for 50 - 64 Kg, 5 tablets for 65 - 75 Kg and 6 tablets for >75 Kg) as a fixed-dose combination.
Other Names:
Intensive Phase for 2 months and Continuation phase for 2 months dose: 400 mg for 30 to 64 yrs AND 600 mg for 65 and above years of age.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
TB recurrence free cure
Time Frame: 24 months after treatment
|
The proportion of microbiologically confirmed new PTB patients with TB recurrence free cure among those treated with the 4-month moxifloxacin containing daily regimen.
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24 months after treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse drug reaction
Time Frame: 4 months, at the end of treatment
|
The proportion of PTB patients with adverse drug reactions in those treated with the 4-month moxifloxacin containing daily regimen.
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4 months, at the end of treatment
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TB Sustained treatment Success, failure, death, loss to follow up
Time Frame: 10 months
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The proportion of PTB patients with sustained treatment success, failure, death, lost to follow-up
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10 months
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TB Relapse and Reinfection
Time Frame: 24 months after treatment
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The proportion of patients with TB relapse and TB re-infection based on genotyping
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24 months after treatment
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Dr. Banurekha MBBS., MPH, National Institute for Research in Tuberculosis, Chennai, India
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- 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
- Moxifloxacin
- Rifampin
- Isoniazid
- Pyrazinamide
- Ethambutol
Other Study ID Numbers
- 2021010
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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