Tuberculosis
Conditions
Keywords
tuberculosis, rifampicin, pharmacokinetics, pharmacodynamics
Brief summary
In this phase II clinical trial, the pharmacokinetics, safety and (short-term) efficacy of higher than standard doses rifampicin will be studied during the intensive phase of tuberculosis (TB) treatment. Patients enrolled in this study will either get the standard TB regimen (including 600 mg rifampicin; first study arm), or 900 mg rifampicin plus isoniazid, ethambutol and pyrazinamide in standard dosages (second study arm), or 1200 mg rifampicin plus the other drugs in standard dosages (third study arm). All patients will get the standard TB regimen during the continuation phase of treatment.
Interventions
DRUGRifampicin in higher doses
Rifampicin 900 mg (study arm 2), and rifampicin 1200 mg (study arm 3)
Sponsors
European and Developing Countries Clinical Trials Partnership (EDCTP)
Sanofi
Kilimanjaro Christian Medical Centre, Tanzania
Kibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania
University Centre for Chronic Diseases Dekkerswald, Groesbeek, The Netherlands
National Institute for Public Health and the Environment (RIVM)
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant has a newly diagnosed pulmonary tuberculosis, confirmed by a positive smear of at least two sputum specimens with ZN staining. * Participant is willing to be tested for HIV. * Participant is at least 18, but not more than 65 years of age at the day of the first dosing of study medication. * Participant is admitted to KNTH or KCMC during the intensive phase of TB treatment. * Participant is able and willing to attend to KNTH or KCMC regularly during the continuation phase of TB treatment. * Participant is able to understand and willing to sign the Informed Consent Form prior to screening evaluations. * Female participants should understand that it is important not to get pregnant during the study. They should agree on taking measures to prevent them from getting pregnant during the study. They should agree on taking measures to prevent them from getting pregnant, such as using a contraceptive device or barrier method.
Exclusion criteria
* Participant has been treated with anti-tuberculosis drugs during the past three years. * Participant's body weight is less than 50 kg. * Participant has abnormal liver function test or serum creatinine (defined as levels higher than the upper limit of normal). * Participant has a relevant medical history or current condition that might interfere with drug absorption, distribution, metabolism or excretion (i.e. chronic gastro-intestinal disease, Diabetes Mellitus, renal or hepatic disease, use of concomitant drugs that interfere with the pharmacokinetics of anti-TB drugs). * Participant is on anti-retroviral treatment at inclusion. * Participant has a CD4 count less than 350 cells/mm3. * Participant has a Karnofsky score of less than 40. * Participant is pregnant or breastfeeding. * Participant has a Multi Drug Resistant (MDR)-TB for which another than the standard treatment regimen is needed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters of rifampicin, desacetylrifampicin, isoniazid, pyrazinamide, ethambutol | Steady state, week 6 |
Secondary
| Measure | Time frame |
|---|---|
| Occurrence of adverse events | baseline, week 1, 2, 4, 6, 8, 10, 12 |
| Bacteriological response of Mycobacterium tuberculosis | Almost daily during first 8 weeks |
| Compare accuracy of surrogate markers (SSCC, mRNA, cytokines) with standard two-month sputum conversion marker | Almost daily during first 8 weeks |
| Documenting the occurrence of mixed Mycobacterium tuberculosis strain infections | Almost daily during first 8 weeks |
Countries
Tanzania
Outcome results
None listed