Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis - Full Text View

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

This study is not yet open for participant recruitment.

Verified by African Poverty Related Infection Oriented Research Initiative, September 2008

Sponsors and Collaborators:	African Poverty Related Infection Oriented Research Initiative Kilimanjaro Christian Medical Centre, Tanzania Kibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands. University Lung centre Dekkerswald, Groesbeek, the Netherlands National Institute for Public Health and the Environment (RIVM)
Information provided by:	African Poverty Related Infection Oriented Research Initiative
ClinicalTrials.gov Identifier:	NCT00760149

Purpose

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.

Condition	Intervention	Phase
Tuberculosis	Drug: Rifampicin in higher doses	Phase II

MedlinePlus related topics: Tuberculosis

Drug Information available for: Rifampin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacokinetics/Dynamics Study
Official Title:	Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania.

Further study details as provided by African Poverty Related Infection Oriented Research Initiative:

Primary Outcome Measures:

Pharmacokinetic parameters of rifampicin, desacetylrifampicin, isoniazid, pyrazinamide, ethambutol [ Time Frame: Steady state, week 3 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Occurrence of adverse events [ Time Frame: baseline, week 1, 2, 4, 6, 8, 10, 12 ] [ Designated as safety issue: Yes ]
Bacteriological response of Mycobacterium tuberculosis [ Time Frame: Almost daily during first 8 weeks ] [ Designated as safety issue: No ]
Compare accuracy of surrogate markers (SSCC, mRNA, cytokines) with standard two-month sputum conversion marker [ Time Frame: Almost daily during first 8 weeks ] [ Designated as safety issue: No ]
Documenting the occurrence of mixed Mycobacterium tuberculosis strain infections [ Time Frame: Almost daily during first 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	February 2009
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator 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.	Drug: Rifampicin in higher doses Rifampicin 900 mg (study arm 2), and rifampicin 1200 mg (study arm 3)
2: Active Comparator 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.	Drug: Rifampicin in higher doses Rifampicin 900 mg (study arm 2), and rifampicin 1200 mg (study arm 3)
3: Active Comparator 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.	Drug: Rifampicin in higher doses Rifampicin 900 mg (study arm 2), and rifampicin 1200 mg (study arm 3)

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00760149

Contacts

Contact: Gibson Kibiki, MD, MMed, PhD	+255 754 572767	gkibiki@gmail.com
Contact: Jossy van den Boogaard, MD	+255 787 148431	jossyvandenboogaard@gmail.com

Locations

Tanzania, Kilimanjaro
Kibong'oto National Tuberculosis Hospital
Sanya Juu, Kilimanjaro, Tanzania, P.O. box 12

Sponsors and Collaborators

African Poverty Related Infection Oriented Research Initiative

Kilimanjaro Christian Medical Centre, Tanzania

Kibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania

Department of Clinical Pharmacy, University Medical Centre St Radboud, The Netherlands.

University Lung centre Dekkerswald, Groesbeek, the Netherlands

National Institute for Public Health and the Environment (RIVM)

Investigators

Principal Investigator:	Rob Aarnoutse, Pharm-D, PhD	Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
Principal Investigator:	Gibson Kibiki, MD, MMed, PhD	Kilimanjaro Christian Medical Centre, Moshi, Tanzania

Responsible Party:	Radboud University Nijmegen Medical Centre, the Netherlands ( Rob Aarnoutse, PharmD, PhD )
Study ID Numbers:	APRIORI 4.1
Study First Received:	September 25, 2008
Last Updated:	September 25, 2008
ClinicalTrials.gov Identifier:	NCT00760149
Health Authority:	The Netherlands: Adviescommissie Mensgebonden Onderzoek (IRB, Radboud University Nijmegen Medical Centre)