Clinical trial NCT00760149: Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis
Official title: Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: tuberculosis
rifampicin
pharmacokinetics
pharmacodynamics
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: European and Developing Countries Clinical Trials Partnership (EDCTP)
name: Sanofi
name: Kilimanjaro Christian Medical Centre, Tanzania
name: Kibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania
name: University Centre for Chronic Diseases Dekkerswald, Groesbeek, The Netherlands
name: National Institute for Public Health and the Environment (RIVM)
First posted: 2008-09-26
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic parameters of rifampicin, desacetylrifampicin, isoniazid, pyrazinamide, ethambutol
timeFrame: Steady state, week 6
Secondary outcomes:
measure: Occurrence of adverse events
timeFrame: baseline, week 1, 2, 4, 6, 8, 10, 12
measure: Bacteriological response of Mycobacterium tuberculosis
timeFrame: Almost daily during first 8 weeks
measure: Compare accuracy of surrogate markers (SSCC, mRNA, cytokines) with standard two-month sputum conversion marker
timeFrame: Almost daily during first 8 weeks
measure: Documenting the occurrence of mixed Mycobacterium tuberculosis strain infections
timeFrame: Almost daily during first 8 weeks
Other outcomes:
Locations:
city: Sanya Juu
country: Tanzania
facility: Kibong'oto National Tuberculosis Hospital
state: Kilimanjaro
Study officials:
affiliation: Radboud University Medical Center
name: Rob Aarnoutse, Pharm-D, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kilimanjaro Christian Medical Centre,Moshi,Tanzania
name: Gibson Kibiki, MD, MMed, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Nijmegen Medical Center/UCCZ Dekkerswald
name: Martin Boeree, MD PhD
role: PRINCIPAL_INVESTIGATOR
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