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

Tuberculosis Clinical Trial

— High RIF  

Official title:

Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00760149
• Other study ID #: APRIORI 4.1
• Secondary ID: PACTR20090600014
• Status: Completed
• Phase: Phase 2
• First received: September 25, 2008
• Last updated: September 6, 2013
• Start date: July 2010
• Est. completion date: September 2013

Study information

• Verified date: September 2013
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Tazania: Tanzanian Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• Rifampicin in higher doses
Rifampicin 900 mg (study arm 2), and rifampicin 1200 mg (study arm 3)

Locations

Country	Name	City	State
Tanzania	Kibong'oto National Tuberculosis Hospital	Sanya Juu	Kilimanjaro

Sponsors (7)

Lead Sponsor	Collaborator
Radboud University	European and Developing Countries Clinical Trials Partnership (EDCTP), Kibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania, Kilimanjaro Christian Medical Centre, Tanzania, National Institute for Public Health and the Environment (RIVM), Sanofi, University Centre for Chronic Diseases Dekkerswald, Groesbeek, The Netherlands

Country where clinical trial is conducted

Tanzania, 

References & Publications (37)

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* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameters of rifampicin, desacetylrifampicin, isoniazid, pyrazinamide, ethambutol		Steady state, week 6	No
Secondary	Occurrence of adverse events		baseline, week 1, 2, 4, 6, 8, 10, 12	Yes
Secondary	Bacteriological response of Mycobacterium tuberculosis		Almost daily during first 8 weeks	No
Secondary	Compare accuracy of surrogate markers (SSCC, mRNA, cytokines) with standard two-month sputum conversion marker		Almost daily during first 8 weeks	No
Secondary	Documenting the occurrence of mixed Mycobacterium tuberculosis strain infections		Almost daily during first 8 weeks	No