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Phase 3 N=1,931 Randomized Quadruple-blind Treatment

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

Pulmonary Tuberculosis

Enrolled (actual)
1,931
Serious AEs
6.4%
Results posted
May 2015
Primary outcome: Primary: Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ). — 43; 78; 105 participants with failure or relapse

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Moxifloxacin, Ethambutol, Isoniazid, Pyrazinamide & Rifampicin (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Global Alliance for TB Drug Development
Primary completion
Oct 2013

Outcome Measures

OutcomeResultp-value
PRIMARY
Combined Failure of Bacteriological Cure and Relapse Within One Year of Completion of Therapy as Defined by Culture Using Solid Media (Lowenstein-Jensen - LJ).
43; 78; 105
PRIMARY
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)
123; 127; 111
SECONDARY
Combined Failure of Bacteriological Cure and Relapse as Defined by Culture Using Liquid Media (Mycobacteria Growth Indicator Tube-MGIT).
65; 98; 131
SECONDARY
Number of Patients Who Are Culture Negative (Solid LJ Culture)
352; 394; 401
SECONDARY
Number of Patients Who Are Culture Negative (Liquid MGIT Culture)
235; 274; 260
SECONDARY
Time to First Culture Negative Sputum Sample (LJ Solid Media)
6.0; 6.0; 6.0
SECONDARY
Time to First Culture Negative Sputum Sample (MGIT Liquid Media)
11.9; 8.0; 8.0
SECONDARY
Sensitivity Analysis Assuming All Losses to Follow-up and Non-tuberculous Deaths Have an Unfavorable Outcome Using Solid (L-J) Media.
172; 219; 217
SECONDARY
Sensitivity Analyses Assuming All Losses to Follow-up and Non-tuberculous Deaths Have a Favourable Outcome Using Solid (L-J) Media.
87; 132; 132

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.

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).
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00864383). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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