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
|