Four Months Moxifloxacin Containing Daily Regimen Study Among New Pulmonary Tuberculosis Patients

NCT05047055 | Unknown DMC

• 1 other identifier: 2021010
• Study Type: observational
• Target: 550
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis, Pulmonary

Keywords

Pulmonary Tuberculosis

Outcome Measures

Primary Outcomes (1)

• TB recurrence free cure

  The proportion of microbiologically confirmed new PTB patients with TB recurrence free cure among those treated with the 4-month moxifloxacin containing daily regimen.

  24 months after treatment

Secondary Outcomes (3)

• Adverse drug reaction

  4 months, at the end of treatment

• TB Sustained treatment Success, failure, death, loss to follow up

  10 months

• TB Relapse and Reinfection

  24 months after treatment

Study Arms (1)

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.

Drug: Isoniazid; Drug: Rifampicin; Drug: Pyrazinamide; Drug: Ethambutol; Drug: Moxifloxacin

Interventions

Isoniazid DRUG

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.

Also known as: H

Single Group - 4 months moxifloxacin group

Rifampicin DRUG

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.

Also known as: R

Single Group - 4 months moxifloxacin group

Pyrazinamide DRUG

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.

Also known as: Z

Single Group - 4 months moxifloxacin group

Ethambutol DRUG

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.

Also known as: E

Single Group - 4 months moxifloxacin group

Moxifloxacin DRUG

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.

Also known as: M

Single Group - 4 months moxifloxacin group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Newly diagnosed adult sputum smear and or CBNAAT positive pulmonary TB patients

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Tuberculosis Research Centre, India: lead
• Indira Gandhi Government Medical College and Hospital (IGGMCH), Nagpur: collaborator
• King George's Medical University, Lucknow: collaborator
• Mahavir Hospital and Research Centre, Hyderabad: collaborator
• Government Vellore Medical College and Hospital, Adukkamparai: collaborator
• Lok Nayak hospital, New Delhi: collaborator

Study Sites (1)

National Institute for Research in Tuberculosis

Chennai, Tamil Nadu, 600031, India

Location

Biospecimen

Retention: SAMPLES WITH DNA

sputum sample of Mycobacterium Tuberculosis with its DNA will be preserved (Positive sputum isolates at baseline and at the time of TB recurrence will be sent to ICMR-NIRT, Chennai for storage for future genotyping)

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Isoniazid; Protons; Rifampin; Pyrazinamide; Ethambutol; Moxifloxacin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Study Officials

• Dr. Banurekha MBBS., MPH

  National Institute for Research in Tuberculosis, Chennai, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientist E

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 16, 2021
• Study Start: March 15, 2022
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)