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Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis

Information source: Global Alliance for TB Drug Development
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pulmonary Tuberculosis

Intervention: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Global Alliance for TB Drug Development

Official(s) and/or principal investigator(s):
Stephen H Gillespie, MB BCh BAO MD DSc, Study Director, Affiliation: University of St Andrews
Andrew Nunn, BSc MSc, Principal Investigator, Affiliation: MRC Clinical Trials Unit
Sarah K Meredith, MB BS MSc, Principal Investigator, Affiliation: MRC Clinical Trials Unit
Timothy D McHugh, BSc PhD CSi, Principal Investigator, Affiliation: Centre for Medical Microbiology, Royal Free and University College Medical School
Ali Zumla, BSc MBChB MSc PhD, Principal Investigator, Affiliation: Centre for International Health, Royal Free and University College Medical School
Alexander Pym, MB BMRCP PhD, Principal Investigator, Affiliation: Unit for Clinical & Biomedical TB Research, MRC Durban
Peter Mwaba, MB ChB MMed PhD, Principal Investigator, Affiliation: University Teaching Hospital
Noel Sam, MMed MD, Principal Investigator, Affiliation: Kilimanjaro Christian Medical Centre
Andreas Diacon, BM MD, Principal Investigator, Affiliation: Tiervlei Trial Center and University of Stellenbosch
Rodney Dawson, MB ChB FCP, Principal Investigator, Affiliation: Centre for TB Research and Innovation, UCT Lung Institute
Evans Amukoye, MBChB. Mmed (Paediatric), Principal Investigator, Affiliation: Centre for Respiratory Disease Research at KEMRI
Leonard Maboko, MD MSc PhD, Principal Investigator, Affiliation: NIMR - Mbeya Medical Research Programme
Ian Sanne, MBBCH FCP(SA), Principal Investigator, Affiliation: Clinical HIV Research Unit (CHRU), Westdene
Cheryl Louw, MBChB, Principal Investigator, Affiliation: Madibeng Centre For Research, Brits
Mengqui Gao, MD, Principal Investigator, Affiliation: Beijing Tuberculosis and Thoracic Tumor Research Institute
Qing Zhang, MD, Principal Investigator, Affiliation: Shanghai Pulmonary Hospital, Shanghai, China
Xiexiu Wang, MD, Principal Investigator, Affiliation: TB Institute, Tianjin
Aziah Mahayiddin, MD, Principal Investigator, Affiliation: Institute of Respiratory Medicine (IPR) Jalan Pahang, Malaysia
Watchara Boonsawat, MD PhD, Principal Investigator, Affiliation: Srinagarind Hospital, Division of Pulmonary Medicine, Khon Kaen University
Charoen Chuchottaworn, MD, Principal Investigator, Affiliation: Chest Disease Institute (CDI), Ministry of Public Health, Nonthaburi
Pairaj Kateruttanakul, MD, Principal Investigator, Affiliation: Rajavithi Hospital, Division of Pulmonary, Department of Medicine, Bangkok
Gerardo Amaya-Tapia, MD, Principal Investigator, Affiliation: Hospital General de occidente de la secretaria, Seattle, Mexico
Stephen Murray, M.D, PhD, Principal Investigator, Affiliation: Global Alliance for TB Drug Development
Michael Brown, BA, BM, BCh, MRCP, PhD, DTM&H, Principal Investigator, Affiliation: London School of Hygiene and Tropical Medicine
Rakesh Lal, MD, Principal Investigator, Affiliation: Centre for Advanced Lung and Sleep Disorders, New Delhi, India
Rakesh Mittal, MBBS MD, Principal Investigator, Affiliation: Dr. Mittal's Clinic, Balaji Medical Store, New Delhi, India
A K Jain, MBBS FICA, Principal Investigator, Affiliation: Diligent Hospital, New Delhi, India
Mahesh Kapoor, MBBS DTCD, Principal Investigator, Affiliation: A One Hospital, New Delhi, India
D K Chauhan, MBBS, Principal Investigator, Affiliation: Dr. D.K. Chauhan, New Delhi, India
Mahip Saluja, M.D, Principal Investigator, Affiliation: Dr. Mahip Saluja Clinic, Meerut, U.P. India
Neeraj Gupta, MD, Principal Investigator, Affiliation: Dr. Neeraj Gupta, Firozabad ,U.P, India
Subodh Katiyar, MD, Principal Investigator, Affiliation: Dr Subodh, Swaroop Nagar,Kanpur, India
Nirmal K Jain, MD, Principal Investigator, Affiliation: Dr.Nirmal Kumar Jain, Jaipur, India
Komal Gupta, M.D, Principal Investigator, Affiliation: Kilkari , Lucknow , India
Fahad Khan, MD, Principal Investigator, Affiliation: New City Hospital and Trauma Centre, Lucknow, India
Vaibhav Gupta, MD, Principal Investigator, Affiliation: Saanvi MultiSpeciality Clinic, Moradabad, UP, India,
Suraj P Sondhi, MD, Principal Investigator, Affiliation: Dr. S. P. Sondhi Clinic , Meerut U.P India
Siddharth Agarwal, MD, Principal Investigator, Affiliation: Siddharth Nursing Home, Agra, U.P India
Sanjay Teotia, M.D, Principal Investigator, Affiliation: Dr. Sanjay Teotia Clinic, Meerut, U.P , India
S PS Chauhan, MD, Principal Investigator, Affiliation: Dr. SPS Chauhan, Firozabad, U.P-India,
Mahesh Mishra, MD, Principal Investigator, Affiliation: Mahatma Gandhi Medical College& Hospital , Jaipur, India
Ashish Rohatgi, DTCD, Principal Investigator, Affiliation: Ish Medical Centre and Respiratory Lab, New Delhi- India
Om P Rai, MD, Principal Investigator, Affiliation: Guru Tej Bahadur Hospital, Kanpur India
Pawan Varshneya, MD, Principal Investigator, Affiliation: Varshneya Chest Clinic & Eye Care Centre, Aligarh, UP India
R K Garg, MD, Principal Investigator, Affiliation: Dr. R. K. Garg's Clinic, U.P, India
Vinod K Karhana, M.D, Principal Investigator, Affiliation: Prakash Devi Memorial Medical Centre,New Delhi, India
Vijay K Khurana, M.D, Principal Investigator, Affiliation: Ram-Tej Hospital, Agra, India
Surya Kant, MD, FCCP, FNCP, FCAI, Principal Investigator, Affiliation: Dr.Surya Kant, Lucknow, India
Shalini Arya, MD, Principal Investigator, Affiliation: Arya Chest Clinic, Meerut, UP,India
Ashok K Singh, MD, FCCP, FCCS, Principal Investigator, Affiliation: Pulmonary Care and Sleep Clinic, Kanpur, India
Bhanu P Singh, MD, FCCP, Principal Investigator, Affiliation: Surya Chest Foundation, Lucknow India
Chandra P Singh, MD, Principal Investigator, Affiliation: Jigyasa Medical Center,Uttar Pradesh, India
Arun Aggarwal, MD, Principal Investigator, Affiliation: Indra Nursing Home and Maternity Centre, Uttar Pradesh, India
Anjula Bhargava, MS, Principal Investigator, Affiliation: Rajul Nursing Home, Sasni Gate, Aligarh, UP India
Angela Crook, Principal Investigator, Affiliation: MRC Clinical Trials Unit
Salome Charalambous, Principal Investigator, Affiliation: The Aurum Institute, Tembisa Hospital, South Africa
Lerato Mohapi, Principal Investigator, Affiliation: Soweto Perinatal HIV Research Unit, Johannesburg, South Africa
Nesri Padayatchi, Principal Investigator, Affiliation: Caprisa eThakwini Research Facility, Durban, South Africa
Sandy Pillay, Principal Investigator, Affiliation: International Clinical Trials Unit, Durban, South Africa

Summary

REMoxTB is a study for the "Rapid Evaluation of Moxifloxacin in the treatment of sputum smear positive tuberculosis". REMoxTB aims to find and evaluate new drugs and regimens that shorten the duration of tuberculosis therapy. The purpose of REMoxTB is to evaluate the efficacy, safety and acceptability of two moxifloxacin-containing treatment combinations to determine whether substituting ethambutol with moxifloxacin in one combination, and/or substituting isoniazid with moxifloxacin in another combination, makes it possible to reduce the duration of treatment for TB.

Clinical Details

Official title: A Randomised Placebo - Controlled Double Blind Trial Comparing 1) a Two Month Intensive Phase of Ethambutol, Moxifloxacin, Rifampicin, Pyrazinamide Versus the Standard Regimen (Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) and 2) a Treatment Shortening Regimen Comparing Two Months Moxifloxacin, Isoniazid, Rifampicin, Pyrazinamide Followed by Two Months Moxifloxacin, Isoniazid, Rifampicin Versus the Standard Regimen (Two Months Ethambutol, Isoniazid, Rifampicin, Pyrazinamide Followed by Four Months Isoniazid and Rifampicin) for the Treatment of Adults With Pulmonary Tuberculosis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ).

Number of Patients With Grade 3 or 4 Adverse Events (Using a Modified Division of Acquired Immunodeficiency Syndrome National Institute of Allergy and Infectious Diseases [DAIDS] Scale of Adverse Event Reporting)

Secondary outcome:

Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).

Number of Patients Who Are Culture Negative (Solid LJ Culture)

Number of Patients Who Are Culture Negative (Liquid MGIT Culture)

Time to First Culture Negative Sputum Sample (LJ Solid Media)

Time to First Culture Negative Sputum Sample (MGIT Liquid Media)

Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.

Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.

Detailed description: The current recommended treatments for tuberculosis (TB) require a patient to take multiple drugs for six to eight months. Because the course of therapy is long, many patients do not adhere to treatment and as a consequence they have a poor outcome. In these cases either the sputum is not cleared of the bacteria causing tuberculosis, or the disease returns again (called relapse). Response to medication can be monitored during treatment by collecting regular sputum samples and examining these samples by culture, for the organisms that cause tuberculosis. The commonly used drugs to treat tuberculosis are rifampicin, isoniazid, ethambutol and pyrazinamide. Previous studies in animals and in humans suggest that a new drug called moxifloxacin may also be an effective treatment in tuberculosis. Moreover, promising laboratory studies on mice suggest that moxifloxacin may enable the total duration of chemotherapy to be reduced to four months, which would be a significant improvement for patients taking medication for tuberculosis. This study will involve comparisons that are designed to assess whether substituting moxifloxacin for individual drugs in existing treatment combinations will enable tuberculosis treatment to be shortened. Patients selected for the study will be allocated to one of three treatment groups. The first group will be given six months standard treatment. A second group will receive moxifloxacin substituted for ethambutol, as part of a four month regimen, to see whether the shorter treatment is not inferior to the standard six month treatment. The third group will receive moxifloxacin substituted for isoniazid, as part of a four month regimen, to see whether the shorter treatment is not inferior to the standard six month treatment. Hypotheses: 1. In treatment-naïve adults with active pulmonary TB treated with eight weeks of moxifloxacin (M), isoniazid (H), rifampicin (R) and pyrazinamide (Z) (i. e. a standard regimen where moxifloxacin is substituted for ethambutol (E)), followed by nine weeks of moxifloxacin, isoniazid and rifampicin, followed by nine weeks of placebo, the proportion of patients who experience treatment failure or disease relapse in the twelve months following treatment completion will not be inferior to that observed in patients who are treated with a standard regimen (eight weeks of ethambutol, isoniazid, rifampicin and pyrazinamide followed by eighteen weeks of isoniazid plus rifampicin) (Comparison 1). 2. In treatment-naïve adults with active pulmonary TB treated with eight weeks of ethambutol, moxifloxacin, rifampicin and pyrazinamide (i. e. a standard regimen where moxifloxacin is substituted for isoniazid), followed by nine weeks of moxifloxacin and rifampicin followed by nine weeks of placebo, the proportion of patients who experience treatment failure or disease relapse in the twelve months following treatment completion will not be inferior to that observed in patients who are treated with a standard regimen (eight weeks of ethambutol, isoniazid, rifampicin and pyrazinamide followed by eighteen weeks of isoniazid plus rifampicin) (Comparison 2).

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Signed written consent or witnessed oral consent in the case of illiteracy, before

undertaking any trial related activity.

- Two sputum specimens positive for tubercle bacilli on smear microscopy at least one

of which must be processed and positive at the study laboratory.

- Aged 18 years or over.

- No previous anti-tuberculosis chemotherapy.

- A firm home address that is readily accessible for visiting and willingness to inform

the study team of any change of address during the treatment and follow-up period.

- Agreement to participate in the study and to give a sample of blood for HIV testing

(see appendices 1 & 2).

- Pre-menopausal women must be using a barrier form of contraception or be surgically

sterilised or have an IUCD in place.

- Laboratory parameters performed up to 14 days before enrolment.

- Serum aspartate transaminase (AST) and alanine transaminase (ALT) activity less

than 3 times the upper limit of normal.

- Serum total bilirubin level less than 2. 5 times upper limit of normal.

Creatinine clearance (CrCl) level greater than 30 mls/min.

- Haemoglobin level of at least 7. 0 g/dL.

- Platelet count of at least 50x109cells/L.

- Serum potassium greater than 3. 5 mmol/L.

- Negative pregnancy test (women of childbearing potential).

Exclusion Criteria:

- Unable to take oral medication.

- Previously enrolled in this study.

- Received any investigational drug in the past 3 months.

- Received an antibiotic active against M. tuberculosis in the last 14 days

(fluoroquinolones, macrolides, standard anti-tuberculosis drugs).

- Any condition that may prove fatal during the first two months of the study period.

- TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome

- Pre-existing non-tuberculosis disease e. g. diabetes, liver or kidney disease, blood

disorders,peripheral neuritis, chronic diarrhoeal disease in which the current clinical condition of the patient is likely to prejudice the response to, or assessment of treatment.

- Pregnant or breast feeding.

- Suffering from a condition likely to lead to uncooperative behaviour e. g. psychiatric

illness or alcoholism.

- Contraindications to any medications in the study regimens.

- Known to have congenital or sporadic syndromes of QTc prolongation or receiving

concomitant medication reported to increase the QTc interval (e. g. amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine).

- Known allergy to any fluoroquinolone antibiotic or history of tendinopathy associated

with quinolones.

- Patients already receiving anti-retroviral therapy.

- Patients whose initial isolate is shown to be multiple drug resistant (i. e. resistant

to rifampicin and isoniazid) or monoresistant to rifampicin, or resistant to any fluoroquinolone)

- Weight less than 35kg

- HIV infection with CD4 count less than 250 cells/µL.

- End stage liver failure (class Child-Pugh C).

Locations and Contacts

Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China

Shanghai Pulmonary Hospital, Shanghai 200433, China

TB Institute, Tianjin 300041, China

A-One Hospital, Delhi 110087, India

Centre for advanced lung and sleep disorders, New Delhi 110026, India

Diligent Hospital, New Delhi 110062, India

Dr. D.K. Chauhan, New Delhi 110002, India

Dr. Mittal's clinic, New Delhi 110043, India

Ish Medical Centre and Respiratory Lab,, New Delhi, India

Smt Prakash Devi Memorial Medical Centre,, New Delhi, India

Centre for Respiratory Disease Research at KEMRI, Nairobi, Kenya

Institute of Respiratory Medicine (IPR) Jalan Pahang, Kuala Lumpur 53000, Malaysia

Centre for TB Research and Innovation, University of Cape Town Lung Institute, Cape Town 7700, South Africa

Tiervlei Trial Center and University of Stellenbosch, Cape Town, South Africa

Unit for Clinical & Biomedical TB Research, MRC Durban, Durban, South Africa

NIMR Mbeya Medical Research Programme, Mbeya, Tanzania

Kilimanjaro Christian Medical Centre, Moshi, Tanzania

University Teaching Hospital, Lusaka, Zambia

Madibeng centre for Research, 40 Pienaar Street,, Madibeng, Brits 0250, South Africa

Srinagarind Hospital, Division of Pulmonary Medicine, Khon Kaen University, Khon Kaen, Mueang 40200, Thailand

Chest Disease Institute (CDI), Ministry of Public,, Nonthaburi, Mueang 11000, Thailand

Rajavithi Hospital, Division Of Pulmonary Medicine, Bangkok, Phayathai 10400, Thailand

Nirmal Kumar Jain, Jaipur, Rajasthan, India

Mahatma Gandhi Medical College& Hospital, Jaipur, Rajsthan, India

Hospital General de Occidente de la secretaria, Guadalajara, Seattle 45170, Mexico

Ram-Tej Hospital,, Agra, Uttar Pradesh, India

Rajul Nursing Home, Aligarh, Uttar Pradesh, India

Varshneya Chest Clinic & Eye Care Centre, Aligarh, Uttar Pradesh, India

Dr. Neeraj Gupta Clinic, Firozabad, Uttar Pradesh, India

S.P.S Chauhan Clinic, Firozabad, Uttar Pradesh, India

Dr. R. K. Garg's Clinic,, Gaziabad, Uttar Pradesh 2011002, India

Indra Nursing Home and Maternity Centre, Ghaziabad, Uttar Pradesh, India

Dr. AK Singh Clinic, Kanpur, Uttar Pradesh, India

Dr. S. K. Katiyar, Swaroop Nagar,, Kanpur, Uttar Pradesh, India

Guru Tej Bahadur Hospital, Kanpur, Uttar Pradesh, India

Dr. Komal Gupta, Lucknow, Uttar Pradesh, India

New City Hospital and Trauma Centre,, Lucknow, Uttar Pradesh, India

Surya Chest Foundation,, Lucknow, Uttar Pradesh, India

Surya Kant Clinic, Lucknow, Uttar Pradesh, India

Dr. Mahip Saluja Clinic, U.P., Meerut,, Uttar Pradesh, India

Arya Chest Clinic, UP,India, Meerut, Uttar Pradesh, India

Dr. S. P. Sondhi Clinic,, Meerut, Uttar Pradesh, India

Sri Ram Plaza, Meerut, Uttar Pradesh, India

Jigyasa Medical Center, Moradabad, Uttar Pradesh, India

Saanvi MultiSpeciality Clinic,, Moradabad, Uttar Pradesh, India

Siddharth Nursing Home,, Agra, Uttar pradesh, India

Clinical HIV Research Unit (CHRU), Johannesburg, Westdene 2092, South Africa

Additional Information

Starting date: January 2008
Last updated: May 7, 2015

Page last updated: August 23, 2015

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