Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis

Phase 2

Completed

• Conditions: Tuberculosis
• Interventions: Drug: Rifampicin in higher doses

• Registration Number: NCT00760149
• Lead Sponsor: Radboud University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-09-25
• Study First Submitted QC: 2008-09-25
• Study First Posted: 2008-09-26
• Study Start: 2010-07
• Status Verified: 2013-09
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Last Update Submitted: 2013-09-06
• Last Update Posted: 2013-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Rifampicin in higher doses	50 patients, treated with rifampicin (900 mg), and the other drugs in standard dosages (isoniazid (300 mg), pyrazinamide (30 mg/kg), ethambutol (15 mg/kg)), administered daily, orally, during the intensive phase of TB treatment. In addition they will receive 1 placebo tablet resembling rifampicin 300 mg.
1	Rifampicin in higher doses	50 patients, treated with the standard anti-TB regimen, including rifampicin (600 mg), isoniazid (300 mg), pyrazinamide (30 mg/kg), ethambutol (15 mg/kg), administered daily, orally, during the intensive phase of TB treatment. In addition they will receive 2 placebo tablets resembling rifampicin 300 mg.
3	Rifampicin in higher doses	50 patients, treated with rifampicin (1200 mg), and the other drugs in standard dosages (isoniazid (300 mg), pyrazinamide (30 mg/kg), ethambutol (15 mg/kg)), administered daily, orally, during the intensive phase of TB treatment.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic parameters of rifampicin, desacetylrifampicin, isoniazid, pyrazinamide, ethambutol	Steady state, week 6

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Kibong'oto National Tuberculosis Hospital; 🇹🇿 Sanya Juu, Kilimanjaro, Tanzania