Pulmonary TuberculosisPhase 3REMoxTBNCT00864383

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

A Phase 3 study testing Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin in people with Pulmonary Tuberculosis, run by Global Alliance for TB Drug Development at 47 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Pulmonary Tuberculosis
What is being tested?: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,931 participants
Where: 47 sitesin 9 countries
Study dates: Jan 2008to Feb 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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).

Show all 14Show fewer

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).

Who cannot join

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

Show all 17Show fewer

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).

Trial locations and contacts

47 sites in 9 countries.

Country

City, postcode or hospital

47 sites in 9 countries

India30 sites

Ram-Tej Hospital,
Agra, Uttar Pradesh
Siddharth Nursing Home,
Agra, Uttar Pradesh
Rajul Nursing Home
Aligarh, Uttar Pradesh
Varshneya Chest Clinic & Eye Care Centre
Aligarh, Uttar Pradesh
A-One Hospital
Delhi, 110087
Dr. Neeraj Gupta Clinic
Firozabad, Uttar Pradesh
S.P.S Chauhan Clinic
Firozabad, Uttar Pradesh
Dr. R. K. Garg's Clinic,
Ghaziabad, Uttar Pradesh, 2011002
Indra Nursing Home and Maternity Centre
Ghaziabad, Uttar Pradesh
Nirmal Kumar Jain
Jaipur, Rajasthan
Mahatma Gandhi Medical College& Hospital
Jaipur, Rajsthan
Dr. AK Singh Clinic
Kanpur, Uttar Pradesh
Dr. S. K. Katiyar, Swaroop Nagar,
Kanpur, Uttar Pradesh
Guru Tej Bahadur Hospital
Kanpur, Uttar Pradesh
Dr. Komal Gupta
Lucknow, Uttar Pradesh
New City Hospital and Trauma Centre,
Lucknow, Uttar Pradesh
Surya Chest Foundation,
Lucknow, Uttar Pradesh
Surya Kant Clinic
Lucknow, Uttar Pradesh
Arya Chest Clinic, UP,India
Meerut, Uttar Pradesh
Dr. Mahip Saluja Clinic, U.P.
Meerut, Uttar Pradesh
Dr. S. P. Sondhi Clinic,
Meerut, Uttar Pradesh
Sri Ram Plaza
Meerut, Uttar Pradesh
Jigyasa Medical Center
Morādābād, Uttar Pradesh
Saanvi MultiSpeciality Clinic,
Morādābād, Uttar Pradesh
Dr. D.K. Chauhan
New Delhi, 110002
Centre for advanced lung and sleep disorders
New Delhi, 110026
Dr. Mittal's clinic
New Delhi, 110043
Diligent Hospital
New Delhi, 110062
Ish Medical Centre and Respiratory Lab,
New Delhi
Smt Prakash Devi Memorial Medical Centre,
New Delhi

Other trials in India

South Africa5 sites

Centre for TB Research and Innovation, University of Cape Town Lung Institute
Cape Town, 7700
Tiervlei Trial Center and University of Stellenbosch
Cape Town
Unit for Clinical & Biomedical TB Research, MRC Durban
Durban
Clinical HIV Research Unit (CHRU)
Johannesburg, Westdene, 2092
Madibeng centre for Research, 40 Pienaar Street,
Madibeng, Brits, 0250

Other trials in South Africa

China3 sites

Beijing Tuberculosis and Thoracic Tumor Research Institute
Beijing, 101149
Shanghai Pulmonary Hospital
Shanghai, 200433
TB Institute
Tianjin, 300041

Other trials in China

Thailand3 sites

Rajavithi Hospital, Division Of Pulmonary Medicine
Bangkok, Phayathai, 10400
Srinagarind Hospital, Division of Pulmonary Medicine, Khon Kaen University
Khon Kaen, Mueang, 40200
Chest Disease Institute (CDI), Ministry of Public,
Nonthaburi, Mueang, 11000

Other trials in Thailand

Tanzania2 sites

NIMR Mbeya Medical Research Programme
Mbeya
Kilimanjaro Christian Medical Centre
Moshi

Other trials in Tanzania

Kenya1 site

Centre for Respiratory Disease Research at KEMRI
Nairobi

Other trials in Kenya

Malaysia1 site

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

Other trials in Malaysia

Mexico1 site

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

Other trials in Mexico

Zambia1 site

University Teaching Hospital
Lusaka

Other trials in Zambia

About this study

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

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.

Read the 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:

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).
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).

Conditions: Pulmonary Tuberculosis
Being tested: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Medical subject headings: Tuberculosis, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & RifampicinDrug
Also called Avelox, Avelon, Avalox, Myambutol
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.

Study groups in NCT00864383
Study group	Role	What they receive
Regimen 1 - 2EHRZ/4HR (control regimen)	Placebo comparator	* 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. Receives: Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Regimen 2 - 2MHRZ/2MHR	Experimental	* 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. Receives: Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin
Regimen 3 - 2EMRZ/2MR	Experimental	* 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 Receives: Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 18 months (within one year of completion of therapy)

Secondary outcomes (7)

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.
Measured: 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.
Measured: 8 weeks
Number of Patients Who Are Culture Negative (Liquid MGIT Culture)
Number of patients who are TB MGIT culture negative at 8 weeks.
Measured: 8 weeks
Time to First Culture Negative Sputum Sample (LJ Solid Media)
Culture negative for TB using LJ cultures.
Measured: 18 months
Time to First Culture Negative Sputum Sample (MGIT Liquid Media)
Measured: 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.
Measured: 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.
Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008Feb 2014

First posted18 Mar 2009 (estimated)
Study startJan 2008
Primary completionOct 2013
Study completionFeb 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Pulmonary TuberculosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,931 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00864383
Sponsor's protocol ID: REMoxTB
Other IDs: ISRCTN85595810
Acronym: REMoxTB
Status last verified: Feb 2017
First submitted: 17 Mar 2009
Last updated: 21 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 24461758
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.
PubMed 24429244
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.
PubMed 25196020
Weir IR, Dufault SM, Phillips PPJ. Estimands for clinical endpoints in tuberculosis treatment randomized controlled trials: a retrospective application in a completed trial. Trials. 2024 Mar 12;25(1):180. doi: 10.1186/s13063-024-07999-w.
PubMed 38468320
Weir IR, Dufault SM, Phillips PP. Estimands for clinical endpoints in Tuberculosis treatment randomized controlled trials: a retrospective application in a completed trial. Res Sq [Preprint]. 2023 Nov 9:rs.3.rs-3486707. doi: 10.21203/rs.3.rs-3486707/v1.
PubMed 37986887
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.
PubMed 29779774
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.
PubMed 26847437

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
Active, not recruitingObservational study
Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma
Nontuberculous Mycobacteria, Mycobacterium Tuberculosis
RecruitingPhase 2
BRIGHT-Child TB: Short-Course Treatment for Non-Severe Pulmonary Tuberculosis in Children
Tuberculosis
RecruitingPhase 3
A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis
Rifampicin-Resistant Pulmonary Tuberculosis, Multidrug-Resistant Pulmonary Tuberculosis
Recruiting
Channa Striata and Curcuma Domestica Supplementation in Patients With Active Pulmonary Tuberculosis
Pulmonary Tuberculosis

All Pulmonary Tuberculosis trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00864383
Acronym / sponsor ID: REMoxTB / REMoxTB
Conditions: Pulmonary Tuberculosis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,931 participants (actual)
Lead sponsor: Global Alliance for TB Drug DevelopmentUniversity, hospital or other
Collaborators: European and Developing Countries Clinical Trials Partnership (EDCTP), University College, London, Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma, Sanofi
Study start: Jan 2008
Primary completion: Oct 2013 (actual)
Study completion: Feb 2014 (actual)
First posted: 18 Mar 2009 (estimated)
Results: Posted 25 May 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Hypotheses:

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).
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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Regimen 1 - 2EHRZ/4HR (control regimen)	Placebo comparator	Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin* 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.
Regimen 2 - 2MHRZ/2MHR	Experimental	Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin* 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.
Regimen 3 - 2EMRZ/2MR	Experimental	Drug: Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin* 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

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.

Key exclusion criteria (17 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & RifampicinAlso: Avelox, Avelon, Avalox, MyambutolMoxifloxacin 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.	Drug	Regimen 1 - 2EHRZ/4HR (control regimen), Regimen 2 - 2MHRZ/2MHR, Regimen 3 - 2EMRZ/2MR

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).
Time frame: 18 months (within one year of completion of therapy)
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.
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)
Time frame: 18 months (within one year of completion of therapy)
The number of participants includes all patients who had at least one grade 3 or 4 adverse event.

7 secondary outcomes

Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).
Time frame: 18 months (within one year of completion of therapy)
Number of Patients Who Are Culture Negative (Solid LJ Culture)
Time frame: 8 weeks
Number of Patients Who Are Culture Negative (Liquid MGIT Culture)
Time frame: 8 weeks
Time to First Culture Negative Sputum Sample (LJ Solid Media)
Time frame: 18 months
Time to First Culture Negative Sputum Sample (MGIT Liquid Media)
Time frame: 18 months
Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.
Time frame: 18 months
Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.
Time frame: 18 months

Results and safety

Results posted to the registry on 25 May 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Regimen 1 - 2EHRZ/4HR (Control Regimen)	640	510
Regimen 2 - 2MHRZ/2MHR	655	514
Regimen 3 - 2EMRZ/2MR	636	524

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).

Time frame: 18 months (within one year of completion of therapy). Number. Unit: participants with failure or relapse

Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n = 510	Regimen 2 - 2MHRZ/2MHR n = 514	Regimen 3 - 2EMRZ/2MR n = 524
Value	43	78	105

Regimen 1 - 2EHRZ/4HR (Control Regimen) vs Regimen 2 - 2MHRZ/2MHR: Adjusted difference in proportions: 6.1 (97.5% CI 1.7 to 10.5)
Regimen 1 - 2EHRZ/4HR (Control Regimen) vs Regimen 3 - 2EMRZ/2MR: Adjusted difference from control: 11.4 (97.5% CI 6.7 to 16.1)

Population analysed: Per protocol population

Primary outcome: 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)

Time frame: 18 months (within one year of completion of therapy). Number. Unit: participants with Grade 3 or 4 AEs

Measure	Regimen 1 - 2EHRZ/4HR (Control Regimen) n = 639	Regimen 2 - 2MHRZ/2MHR n = 655	Regimen 3 - 2EMRZ/2MR n = 636
Value	123	127	111

Population analysed: Safety population, defined as all subjects who underwent randomization and who received at least on dose of study drug.

7 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Regimen 1 - 2EHRZ/4HR (Control Regimen)	38 of 639 (5.9%)	507 of 639 (79.3%)	Not reported
Regimen 2 - 2MHRZ/2MHR	46 of 655 (7%)	537 of 655 (82%)	Not reported
Regimen 3 - 2EMRZ/2MR	40 of 636 (6.3%)	522 of 636 (82.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24461758Bryant 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.
Background: PubMed 24429244Friedrich 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.
Results publication: PubMed 25196020Gillespie 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.
Derived from this study: PubMed 38468320Weir IR, Dufault SM, Phillips PPJ. Estimands for clinical endpoints in tuberculosis treatment randomized controlled trials: a retrospective application in a completed trial. Trials. 2024 Mar 12;25(1):180. doi: 10.1186/s13063-024-07999-w.
Derived from this study: PubMed 37986887Weir IR, Dufault SM, Phillips PP. Estimands for clinical endpoints in Tuberculosis treatment randomized controlled trials: a retrospective application in a completed trial. Res Sq [Preprint]. 2023 Nov 9:rs.3.rs-3486707. doi: 10.21203/rs.3.rs-3486707/v1.
Derived from this study: PubMed 29779774Rachow 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.
Derived from this study: PubMed 26847437Phillips 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.

Related trials for Pulmonary Tuberculosis

RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
Active, not recruitingObservational study
Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma
Nontuberculous Mycobacteria, Mycobacterium Tuberculosis
RecruitingPhase 2
BRIGHT-Child TB: Short-Course Treatment for Non-Severe Pulmonary Tuberculosis in Children
Tuberculosis
RecruitingPhase 3
A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis
Rifampicin-Resistant Pulmonary Tuberculosis, Multidrug-Resistant Pulmonary Tuberculosis
Recruiting
Channa Striata and Curcuma Domestica Supplementation in Patients With Active Pulmonary Tuberculosis
Pulmonary Tuberculosis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stephen H Gillespie, MB BCh BAO MD DSc study director

University of St Andrews

Andrew Nunn, BSc MSc principal investigator

MRC Clinical Trials Unit

Sarah K Meredith, MB BS MSc principal investigator

MRC Clinical Trials Unit

47 sites in 9 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 sites in India, South Africa, China, Thailand, Tanzania and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). (time frame: 18 months (within one year of completion of therapy)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00864383, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2017.