Clinical trial NCT05047055: Four Months Moxifloxacin Containing Daily Regimen Study Among New Pulmonary Tuberculosis Patients
Official title: 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
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Tuberculosis, Pulmonary
Keywords: Pulmonary Tuberculosis
Lead sponsor: Tuberculosis Research Centre, India
Sponsor class: OTHER_GOV
Collaborators: name: Indira Gandhi Government Medical College and Hospital (IGGMCH), Nagpur
name: King George's Medical University, Lucknow
name: Mahavir Hospital and Research Centre, Hyderabad
name: Government Vellore Medical College and Hospital, Adukkamparai
name: Lok Nayak hospital, New Delhi
First posted: 2021-09-16
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Newly diagnosed adult sputum smear and or CBNAAT positive pulmonary TB patients

Brief summary: 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.

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:

1. To determine the Adverse drug reactions (ADR) with the 4-month moxifloxacin containing daily regimen
2. To determine to response to treatment with the 4-month moxifloxacin containing daily regimen
3. 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

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 65 years
2. At least one sputum smear and or CBNAAT test should be positive for tubercle bacilli
3. 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.
4. Willing to follow the trial procedures
5. Willing to give written informed consent
6. Residing within the study TU

Exclusion Criteria:

1. Body weight less than 30 kg
2. 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
3. Multidrug resistant TB (MDR-TB)
4. Resistance to isoniazid or rifampicin or quinolone as evidenced by Cartridge based Nucleic acid Amplification test (CBNAAT) and Line probe Assay (LPA) test
5. Associated extra-pulmonary TB except TB superficial lymphadenitis
6. 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.
7. QTcF\> 450 ms or bundle branch block or heart block on ECG
8. Psychiatric illness
9. Seizure disorder
10. Pregnancy or lactation
11. Those seriously ill as defined by a score of \<50 on Karnofsky scale (Annexure 1)

Primary outcomes:
measure: TB recurrence free cure
timeFrame: 24 months after treatment
Secondary outcomes:
measure: Adverse drug reaction
timeFrame: 4 months, at the end of treatment
measure: TB Sustained treatment Success, failure, death, loss to follow up
timeFrame: 10 months
measure: TB Relapse and Reinfection
timeFrame: 24 months after treatment
Other outcomes:
Locations:
city: Chennai
country: India
facility: National Institute for Research in Tuberculosis
state: Tamilnadu
Study officials:
affiliation: National Institute for Research in Tuberculosis, Chennai, India
name: Dr. Banurekha MBBS., MPH
role: PRINCIPAL_INVESTIGATOR
References: