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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Tuberculosis
• Intervention / Treatment: Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin

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).

• Study Type: Interventional
• Enrollment (Actual): 1931
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 101149
    • Beijing Tuberculosis and Thoracic Tumor Research Institute
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
  • Tianjin, China, 300041
    • TB Institute
• India
  • Delhi, India, 110087
    • A-One Hospital
  • New Delhi, India, 110002
    • Dr. D.K. Chauhan
  • New Delhi, India, 110026
    • Centre for advanced lung and sleep disorders
  • New Delhi, India, 110043
    • Dr. Mittal's clinic
  • New Delhi, India, 110062
    • Diligent Hospital
  • New Delhi, India
    • Ish Medical Centre and Respiratory Lab,
  • New Delhi, India
    • Smt Prakash Devi Memorial Medical Centre,
  • Rajasthan
    • Jaipur, Rajasthan, India
      • Nirmal Kumar Jain
  • Rajsthan
    • Jaipur, Rajsthan, India
      • Mahatma Gandhi Medical College& Hospital
  • Uttar Pradesh
    • Agra, Uttar Pradesh, India
      • Ram-Tej Hospital,
    • Aligarh, Uttar Pradesh, India
      • Rajul Nursing Home
    • Aligarh, Uttar Pradesh, India
      • Varshneya Chest Clinic & Eye Care Centre
    • Firozabad, Uttar Pradesh, India
      • Dr. Neeraj Gupta Clinic
    • Firozabad, Uttar Pradesh, India
      • S.P.S Chauhan Clinic
    • Gaziabad, Uttar Pradesh, India, 2011002
      • Dr. R. K. Garg's Clinic,
    • Ghaziabad, Uttar Pradesh, India
      • Indra Nursing Home and Maternity Centre
    • Kanpur, 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
    • Lucknow, 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
    • 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
      • Dr. Mahip Saluja Clinic, U.P.
    • Moradabad, Uttar Pradesh, India
      • Jigyasa Medical Center
    • Moradabad, Uttar Pradesh, India
      • Saanvi MultiSpeciality Clinic,
  • Uttar pradesh
    • Agra, Uttar pradesh, India
      • Siddharth Nursing Home,
• Kenya
  • Nairobi, Kenya
    • Centre for Respiratory Disease Research at KEMRI
• Malaysia
  • Kuala Lumpur, Malaysia, 53000
    • Institute of Respiratory Medicine (IPR) Jalan Pahang
• Mexico
  • Seattle
    • Guadalajara, Seattle, Mexico, 45170
      • Hospital General de Occidente de la secretaria
• South Africa
  • Cape Town, South Africa, 7700
    • Centre for TB Research and Innovation, University of Cape Town Lung Institute
  • Cape Town, South Africa
    • Tiervlei Trial Center and University of Stellenbosch
  • Durban, South Africa
    • Unit for Clinical & Biomedical TB Research, MRC Durban
  • Brits
    • Madibeng, Brits, South Africa, 0250
      • Madibeng centre for Research, 40 Pienaar Street,
  • Westdene
    • Johannesburg, Westdene, South Africa, 2092
      • Clinical HIV Research Unit (CHRU)
• Tanzania
  • Mbeya, Tanzania
    • NIMR Mbeya Medical Research Programme
  • Moshi, Tanzania
    • Kilimanjaro Christian Medical Centre
• Thailand
  • Mueang
    • Khon Kaen, Mueang, Thailand, 40200
      • Srinagarind Hospital, Division of Pulmonary Medicine, Khon Kaen University
    • Nonthaburi, Mueang, Thailand, 11000
      • Chest Disease Institute (CDI), Ministry of Public,
  • Phayathai
    • Bangkok, Phayathai, Thailand, 10400
      • Rajavithi Hospital, Division Of Pulmonary Medicine
• Zambia
  • Lusaka, Zambia
    • University Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Regimen 1 - 2EHRZ/4HR (control regimen); Eight weeks of chemotherapy with Ethambutol, Isoniazid, Rifampicin and Pyrazinamide plus the Moxifloxacin placebo, followed by; Nine weeks of Isoniazid and Rifampicin plus the Moxifloxacin placebo, followed by; Nine weeks of Isoniazid and Rifampicin only.	Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin; Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.; Other Names: Avelox; Rifampin; Rifadin; Myambutol; Avalox; Avelon; Nydrazid
Experimental: Regimen 2 - 2MHRZ/2MHR; Eight weeks of chemotherapy with Moxifloxacin, Isoniazid, Rifampicin and Pyrazinamide plus the Ethambutol placebo, followed by; Nine weeks of Moxifloxacin, Isoniazid and Rifampicin, followed by; Nine weeks of the Isoniazid placebo and the Rifampicin placebo.	Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin; Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.; Other Names: Avelox; Rifampin; Rifadin; Myambutol; Avalox; Avelon; Nydrazid
Experimental: Regimen 3 - 2EMRZ/2MR; Eight weeks of chemotherapy with Ethambutol, Moxifloxacin, Rifampicin and Pyrazinamide plus the Isoniazid placebo, followed by; Nine weeks of Moxifloxacin and Rifampicin plus the Isoniazid placebo, followed by; Nine weeks of the Isoniazid placebo and the Rifampicin placebo	Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin; Moxifloxacin 400 mg Rifampicin < 45 kg 450 mg > 45 kg 600 mg Isoniazid 300 mg Pyrazinamide < 40 kg 25 mg/kg rounded to nearest 500 mg* 40-55 kg 1000 mg > 55 kg - 75 kg 1500 mg > 75 kg 2000 mg Ethambutol < 40 kg 15 mg/kg rounded to nearest 100 mg 40-55 kg 800 mg > 55 kg - 75 kg 1200 mg > 75 kg 1600 mg *For pyrazinamide dosing in patients < 40 kg, 1000 mg used instead of 500 mg All treatment is taken daily, for a duration of up to 26 weeks depending on treatment arm.; Other Names: Avelox; Rifampin; Rifadin; Myambutol; Avalox; Avelon; Nydrazid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ).	The primary efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome). Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis. For the final 18 month study visit when both L-J samples were contaminated or missing, if the subject could not be brought back, liquid medium culture results were used in place of solid medium culture results.	18 months (within one year of completion of therapy)
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)	The number of participants includes all patients who had at least one grade 3 or 4 adverse event.	18 months (within one year of completion of therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).	The secondary analysis of efficacy outcome was the proportion of patients who had bacteriologically or clinically defined failure or relapse within 18 months after randomization (a composite unfavorable outcome) based on MGIT. Culture-negative status was defined as two negative-culture results at different visits without an intervening positive result. The date of culture-negative status was defined as the date of the first negative-culture result. This status continued until there were two positive cultures, without an intervening negative culture, or until there was a single positive culture that was not followed by two negative cultures. Relapse strains were those shown to be identical on 24-locus Mycobacterial interspersed repetitive units (MIRU) analysis.	18 months (within one year of completion of therapy)
Number of Patients Who Are Culture Negative (Solid LJ Culture)	Number of patients who are TB LJ culture negative at 8 weeks.	8 weeks
Number of Patients Who Are Culture Negative (Liquid MGIT Culture)	Number of patients who are TB MGIT culture negative at 8 weeks.	8 weeks
Time to First Culture Negative Sputum Sample (LJ Solid Media)	Culture negative for TB using LJ cultures.	18 months
Time to First Culture Negative Sputum Sample (MGIT Liquid Media)		18 months
Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.	Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Unfavorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result ("isolated positive culture") was followed by at least two negative culture results.	18 months
Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.	Sensitivity Analysis of Primary Efficacy Results of All Randomized Subjects Imputing Favorable for Missing Outcomes. Analysis is the number of subjects with an unfavorable outcome. Favorable outcome is defined as the number of subjects with a negative TB culture status at 18 months (at or after 72 weeks), who had not already been classified as having an unfavorable outcome, and whose last positive TB culture result ("isolated positive culture") was followed by at least two negative culture results.	18 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Bryant JM, Harris SR, Parkhill J, Dawson R, Diacon AH, van Helden P, Pym A, Mahayiddin AA, Chuchottaworn C, Sanne IM, Louw C, Boeree MJ, Hoelscher M, McHugh TD, Bateson AL, Hunt RD, Mwaigwisya S, Wright L, Gillespie SH, Bentley SD. Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study. Lancet Respir Med. 2013 Dec;1(10):786-92. doi: 10.1016/S2213-2600(13)70231-5. Epub 2013 Nov 21.
• Friedrich SO, Rachow A, Saathoff E, Singh K, Mangu CD, Dawson R, Phillips PP, Venter A, Bateson A, Boehme CC, Heinrich N, Hunt RD, Boeree MJ, Zumla A, McHugh TD, Gillespie SH, Diacon AH, Hoelscher M; Pan African Consortium for the Evaluation of Anti-tuberculosis Antibiotics (PanACEA). Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment. Lancet Respir Med. 2013 Aug;1(6):462-70. doi: 10.1016/S2213-2600(13)70119-X. Epub 2013 Jul 1.
• Gillespie SH, Crook AM, McHugh TD, Mendel CM, Meredith SK, Murray SR, Pappas F, Phillips PP, Nunn AJ; REMoxTB Consortium. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014 Oct 23;371(17):1577-87. doi: 10.1056/NEJMoa1407426. Epub 2014 Sep 7.
• Rachow A, Saathoff E, Mtafya B, Mapamba D, Mangu C, Rojas-Ponce G, Ntinginya NE, Boeree M, Heinrich N, Gillespie SH, Hoelscher M; PanACEA-Consortium. The impact of repeated NALC/NaOH- decontamination on the performance of Xpert MTB/RIF assay. Tuberculosis (Edinb). 2018 May;110:56-58. doi: 10.1016/j.tube.2018.04.001. Epub 2018 Apr 5.
• Phillips PP, Mendel CM, Burger DA, Crook AM, Nunn AJ, Dawson R, Diacon AH, Gillespie SH. Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. BMC Med. 2016 Feb 4;14:19. doi: 10.1186/s12916-016-0565-y. Erratum In: BMC Med. 2016;14:36. Crook, Angela [corrected to Crook, Angela M].

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (Estimate): March 18, 2009

Study Record Updates

• Last Update Posted (Actual): March 21, 2017
• Last Update Submitted That Met QC Criteria: February 15, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• 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: REMoxTB; ISRCTN85595810