Clinical trial NCT00864383: Controlled Comparison of Two Moxifloxacin Containing Treatment Shortening Regimens in Pulmonary Tuberculosis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Tuberculosis
Lead sponsor: Global Alliance for TB Drug Development
Sponsor class: OTHER
Collaborators: name: European and Developing Countries Clinical Trials Partnership (EDCTP)
name: University College, London
name: Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
name: Sanofi
First posted: 2009-03-18
Enrollment: 1931
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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).

Primary outcomes:
measure: Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ).
timeFrame: 18 months (within one year of completion of therapy)
measure: 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)
timeFrame: 18 months (within one year of completion of therapy)
Secondary outcomes:
measure: Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).
timeFrame: 18 months (within one year of completion of therapy)
measure: Number of Patients Who Are Culture Negative (Solid LJ Culture)
timeFrame: 8 weeks
measure: Number of Patients Who Are Culture Negative (Liquid MGIT Culture)
timeFrame: 8 weeks
measure: Time to First Culture Negative Sputum Sample (LJ Solid Media)
timeFrame: 18 months
measure: Time to First Culture Negative Sputum Sample (MGIT Liquid Media)
timeFrame: 18 months
measure: Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.
timeFrame: 18 months
measure: Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.
timeFrame: 18 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tuberculosis and Thoracic Tumor Research Institute
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Tianjin
country: China
facility: TB Institute
city: Jaipur
country: India
facility: Nirmal Kumar Jain
state: Rajasthan
city: Jaipur
country: India
facility: Mahatma Gandhi Medical College& Hospital
state: Rajsthan
city: Agra
country: India
facility: Ram-Tej Hospital,
state: Uttar Pradesh
city: Agra
country: India
facility: Siddharth Nursing Home,
state: Uttar pradesh
city: Aligarh
country: India
facility: Rajul Nursing Home
state: Uttar Pradesh
city: Aligarh
country: India
facility: Varshneya Chest Clinic & Eye Care Centre
state: Uttar Pradesh
city: Firozabad
country: India
facility: Dr. Neeraj Gupta Clinic
state: Uttar Pradesh
city: Firozabad
country: India
facility: S.P.S Chauhan Clinic
state: Uttar Pradesh
city: Gaziabad
country: India
facility: Dr. R. K. Garg's Clinic,
state: Uttar Pradesh
city: Ghaziabad
country: India
facility: Indra Nursing Home and Maternity Centre
state: Uttar Pradesh
city: Kanpur
country: India
facility: Dr. AK Singh Clinic
state: Uttar Pradesh
city: Kanpur
country: India
facility: Dr. S. K. Katiyar, Swaroop Nagar,
state: Uttar Pradesh
city: Kanpur
country: India
facility: Guru Tej Bahadur Hospital
state: Uttar Pradesh
city: Lucknow
country: India
facility: Dr. Komal Gupta
state: Uttar Pradesh
city: Lucknow
country: India
facility: New City Hospital and Trauma Centre,
state: Uttar Pradesh
city: Lucknow
country: India
facility: Surya Chest Foundation,
state: Uttar Pradesh
city: Lucknow
country: India
facility: Surya Kant Clinic
state: Uttar Pradesh
city: Meerut,
country: India
facility: Dr. Mahip Saluja Clinic, U.P.
state: Uttar Pradesh
city: Meerut
country: India
facility: Arya Chest Clinic, UP,India
state: Uttar Pradesh
city: Meerut
country: India
facility: Dr. S. P. Sondhi Clinic,
state: Uttar Pradesh
city: Meerut
country: India
facility: Sri Ram Plaza
state: Uttar Pradesh
city: Moradabad
country: India
facility: Jigyasa Medical Center
state: Uttar Pradesh
city: Moradabad
country: India
facility: Saanvi MultiSpeciality Clinic,
state: Uttar Pradesh
city: Delhi
country: India
facility: A-One Hospital
city: New Delhi
country: India
facility: Dr. D.K. Chauhan
city: New Delhi
country: India
facility: Centre for advanced lung and sleep disorders
city: New Delhi
country: India
facility: Dr. Mittal's clinic
city: New Delhi
country: India
facility: Diligent Hospital
city: New Delhi
country: India
facility: Ish Medical Centre and Respiratory Lab,
city: New Delhi
country: India
facility: Smt Prakash Devi Memorial Medical Centre,
city: Nairobi
country: Kenya
facility: Centre for Respiratory Disease Research at KEMRI
city: Kuala Lumpur
country: Malaysia
facility: Institute of Respiratory Medicine (IPR) Jalan Pahang
city: Guadalajara
country: Mexico
facility: Hospital General de Occidente de la secretaria
state: Seattle
city: Madibeng
country: South Africa
facility: Madibeng centre for Research, 40 Pienaar Street,
state: Brits
city: Johannesburg
country: South Africa
facility: Clinical HIV Research Unit (CHRU)
state: Westdene
city: Cape Town
country: South Africa
facility: Centre for TB Research and Innovation, University of Cape Town Lung Institute
city: Cape Town
country: South Africa
facility: Tiervlei Trial Center and University of Stellenbosch
city: Durban
country: South Africa
facility: Unit for Clinical & Biomedical TB Research, MRC Durban
city: Mbeya
country: Tanzania
facility: NIMR Mbeya Medical Research Programme
city: Moshi
country: Tanzania
facility: Kilimanjaro Christian Medical Centre
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital, Division of Pulmonary Medicine, Khon Kaen University
state: Mueang
city: Nonthaburi
country: Thailand
facility: Chest Disease Institute (CDI), Ministry of Public,
state: Mueang
city: Bangkok
country: Thailand
facility: Rajavithi Hospital, Division Of Pulmonary Medicine
state: Phayathai
city: Lusaka
country: Zambia
facility: University Teaching Hospital
Study officials:
affiliation: University of St Andrews
name: Stephen H Gillespie, MB BCh BAO MD DSc
role: STUDY_DIRECTOR
affiliation: MRC Clinical Trials Unit
name: Andrew Nunn, BSc MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: MRC Clinical Trials Unit
name: Sarah K Meredith, MB BS MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Medical Microbiology, Royal Free and University College Medical School
name: Timothy D McHugh, BSc PhD CSi
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for International Health, Royal Free and University College Medical School
name: Ali Zumla, BSc MBChB MSc PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unit for Clinical & Biomedical TB Research, MRC Durban
name: Alexander Pym, MB BMRCP PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Teaching Hospital
name: Peter Mwaba, MB ChB MMed PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kilimanjaro Christian Medical Centre
name: Noel Sam, MMed MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tiervlei Trial Center and University of Stellenbosch
name: Andreas Diacon, BM MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for TB Research and Innovation, UCT Lung Institute
name: Rodney Dawson, MB ChB FCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Respiratory Disease Research at KEMRI
name: Evans Amukoye, MBChB. Mmed (Paediatric)
role: PRINCIPAL_INVESTIGATOR
affiliation: NIMR - Mbeya Medical Research Programme
name: Leonard Maboko, MD MSc PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical HIV Research Unit (CHRU), Westdene
name: Ian Sanne, MBBCH FCP(SA)
role: PRINCIPAL_INVESTIGATOR
affiliation: Madibeng Centre For Research, Brits
name: Cheryl Louw, MBChB
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tuberculosis and Thoracic Tumor Research Institute
name: Mengqui Gao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
name: Qing Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: TB Institute, Tianjin
name: Xiexiu Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Respiratory Medicine (IPR) Jalan Pahang, Malaysia
name: Aziah Mahayiddin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Srinagarind Hospital, Division of Pulmonary Medicine, Khon Kaen University
name: Watchara Boonsawat, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chest Disease Institute (CDI), Ministry of Public Health, Nonthaburi
name: Charoen Chuchottaworn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rajavithi Hospital, Division of Pulmonary, Department of Medicine, Bangkok
name: Pairaj Kateruttanakul, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital General de occidente de la secretaria, Seattle, Mexico
name: Gerardo Amaya-Tapia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Global Alliance for TB Drug Development
name: Stephen Murray, M.D, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London School of Hygiene and Tropical Medicine
name: Michael Brown, BA, BM, BCh, MRCP, PhD, DTM&H
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Advanced Lung and Sleep Disorders, New Delhi, India
name: Rakesh Lal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Mittal's Clinic, Balaji Medical Store, New Delhi, India
name: Rakesh Mittal, MBBS MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diligent Hospital, New Delhi, India
name: A K Jain, MBBS FICA
role: PRINCIPAL_INVESTIGATOR
affiliation: A One Hospital, New Delhi, India
name: Mahesh Kapoor, MBBS DTCD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr D.K. Chauhan, New Delhi, India
name: D K Chauhan, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Mahip Saluja Clinic, Meerut, U.P. India
name: Mahip Saluja, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Neeraj Gupta, Firozabad ,U.P, India
name: Neeraj Gupta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr Subodh, Swaroop Nagar,Kanpur, India
name: Subodh Katiyar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr.Nirmal Kumar Jain, Jaipur, India
name: Nirmal K Jain, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kilkari , Lucknow , India
name: Komal Gupta, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: New City Hospital and Trauma Centre, Lucknow, India
name: Fahad Khan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Saanvi MultiSpeciality Clinic, Moradabad, UP, India,
name: Vaibhav Gupta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. S. P. Sondhi Clinic , Meerut U.P India
name: Suraj P Sondhi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Siddharth Nursing Home, Agra, U.P India
name: Siddharth Agarwal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Sanjay Teotia Clinic, Meerut, U.P , India
name: Sanjay Teotia, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. SPS Chauhan, Firozabad, U.P-India,
name: S PS Chauhan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mahatma Gandhi Medical College& Hospital , Jaipur, India
name: Mahesh Mishra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ish Medical Centre and Respiratory Lab, New Delhi- India
name: Ashish Rohatgi, DTCD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guru Tej Bahadur Hospital, Kanpur India
name: Om P Rai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Varshneya Chest Clinic & Eye Care Centre, Aligarh, UP India
name: Pawan Varshneya, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. R. K. Garg's Clinic, U.P, India
name: R K Garg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Prakash Devi Memorial Medical Centre,New Delhi, India
name: Vinod K Karhana, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Ram-Tej Hospital, Agra, India
name: Vijay K Khurana, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr.Surya Kant, Lucknow, India
name: Surya Kant, MD, FCCP, FNCP, FCAI
role: PRINCIPAL_INVESTIGATOR
affiliation: Arya Chest Clinic, Meerut, UP,India
name: Shalini Arya, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pulmonary Care and Sleep Clinic, Kanpur, India
name: Ashok K Singh, MD, FCCP, FCCS
role: PRINCIPAL_INVESTIGATOR
affiliation: Surya Chest Foundation, Lucknow India
name: Bhanu P Singh, MD, FCCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Jigyasa Medical Center,Uttar Pradesh, India
name: Chandra P Singh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indra Nursing Home and Maternity Centre, Uttar Pradesh, India
name: Arun Aggarwal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rajul Nursing Home, Sasni Gate, Aligarh, UP India
name: Anjula Bhargava, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: MRC Clinical Trials Unit
name: Angela Crook
role: PRINCIPAL_INVESTIGATOR
affiliation: The Aurum Institute, Tembisa Hospital, South Africa
name: Salome Charalambous
role: PRINCIPAL_INVESTIGATOR
affiliation: Soweto Perinatal HIV Research Unit, Johannesburg, South Africa
name: Lerato Mohapi
role: PRINCIPAL_INVESTIGATOR
affiliation: Caprisa eThakwini Research Facility, Durban, South Africa
name: Nesri Padayatchi
role: PRINCIPAL_INVESTIGATOR
affiliation: International Clinical Trials Unit, Durban, South Africa
name: Sandy Pillay
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.