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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
University College, London
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Sanofi
Information provided by (Responsible Party):
Global Alliance for TB Drug Development
ClinicalTrials.gov Identifier:
NCT00864383
First received: March 17, 2009
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Pulmonary Tuberculosis
Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Global Alliance for TB Drug Development:

Primary Outcome Measures:
  • Combined failure of bacteriological cure and relapse within one year of completion of therapy as defined by culture using solid media. [ Time Frame: 18 months (within one year of completion of therapy) ] [ Designated as safety issue: No ]
  • Proportion of patients with grade 3 or 4 adverse events (using a modified DAIDS scale of adverse event reporting) [ Time Frame: 18 months (within one year of completion of therapy) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Combined failure of bacteriological cure and relapse as defined by culture using liquid media [ Time Frame: 18 months (within one year of completion of therapy) ] [ Designated as safety issue: No ]
  • Proportion of patients who are culture negative (solid and liquid media) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Time to first culture negative sputum sample (solid and liquid media) [ Time Frame: Estimated 3 to 6 months ] [ Designated as safety issue: No ]
  • Speed of decline of sputum viable count by culture using solid or liquid media [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Sensitivity analyses assuming all losses to follow-up and non-tuberculous deaths have an unfavourable outcome using both solid and liquid media [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Sensitivity analyses assuming all losses to follow-up and non-tuberculous deaths have a favourable outcome using both solid and liquid media. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 1931
Study Start Date: January 2008
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • Avelon
  • Avalox
  • Myambutol
  • Nydrazid
  • Rifampin
  • Rifadin
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
  • Avelon
  • Avalox
  • Myambutol
  • Nydrazid
  • Rifampin
  • Rifadin
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
  • Avelon
  • Avalox
  • Myambutol
  • Nydrazid
  • Rifampin
  • Rifadin

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00864383

  Show 47 Study Locations
Sponsors and Collaborators
Global Alliance for TB Drug Development
European and Developing Countries Clinical Trials Partnership (EDCTP)
University College, London
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Sanofi
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
  More Information

No publications provided

Responsible Party: Global Alliance for TB Drug Development
ClinicalTrials.gov Identifier: NCT00864383     History of Changes
Other Study ID Numbers: REMoxTB, ISRCTN85595810
Study First Received: March 17, 2009
Last Updated: February 19, 2014
Health Authority: South Africa: Medicines Control Council
Zambia: Pharmaceutical Regulatory Authority
Tanzania: Food & Drug Administration
Kenya: Pharmacy and Poisons Board
China: Ministry of Health
Malaysia: Ministry of Health
Thailand: Food and Drug Administration
India: Ministry of Health
Mexico: Ministry of Health

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Ethambutol
Isoniazid
Pyrazinamide
Rifampin
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Antibiotics, Antitubercular
Enzyme Inhibitors
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Contraceptives, Oral, Combined

ClinicalTrials.gov processed this record on July 20, 2014