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

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ClinicalTrials.gov Identifier: NCT00760149
Recruitment Status : Completed
First Posted : September 26, 2008
Last Update Posted : September 9, 2013
Sponsor:
Collaborators:
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)
Information provided by:
Radboud University Medical Center

Study Description
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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.

Condition or disease Intervention/treatment Phase
Tuberculosis Drug: Rifampicin in higher doses Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacokinetics and Pharmacodynamics of High Versus Standard Dose Rifampicin in Patients With Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania.
Study Start Date : July 2010
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis
Drug Information available for: Rifampin

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: 1
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)
Active Comparator: 2
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)
Active Comparator: 3
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)


Outcome Measures
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Primary Outcome Measures :
  1. Pharmacokinetic parameters of rifampicin, desacetylrifampicin, isoniazid, pyrazinamide, ethambutol [ Time Frame: Steady state, week 6 ]

Secondary Outcome Measures :
  1. Occurrence of adverse events [ Time Frame: baseline, week 1, 2, 4, 6, 8, 10, 12 ]
  2. Bacteriological response of Mycobacterium tuberculosis [ Time Frame: Almost daily during first 8 weeks ]
  3. Compare accuracy of surrogate markers (SSCC, mRNA, cytokines) with standard two-month sputum conversion marker [ Time Frame: Almost daily during first 8 weeks ]
  4. Documenting the occurrence of mixed Mycobacterium tuberculosis strain infections [ Time Frame: Almost daily during first 8 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00760149


Locations
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Tanzania
Kibong'oto National Tuberculosis Hospital
Sanya Juu, Kilimanjaro, Tanzania, P.O. box 12
Sponsors and Collaborators
Radboud University Medical Center
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)
Investigators
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Principal Investigator: Rob Aarnoutse, Pharm-D, PhD Radboud University Medical Center
Principal Investigator: Gibson Kibiki, MD, MMed, PhD Kilimanjaro Christian Medical Centre,Moshi,Tanzania
Principal Investigator: Martin Boeree, MD PhD Radboud University Nijmegen Medical Center/UCCZ Dekkerswald
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Rob Aarnoutse, PharmD, PhD, Radboud University Nijmegen Medical Centre, the Netherlands
ClinicalTrials.gov Identifier: NCT00760149    
Other Study ID Numbers: APRIORI 4.1
PACTR2009060001493909 ( Registry Identifier: www.pactr.org )
First Posted: September 26, 2008    Key Record Dates
Last Update Posted: September 9, 2013
Last Verified: September 2013
Keywords provided by Radboud University Medical Center:
tuberculosis
rifampicin
pharmacokinetics
pharmacodynamics
Additional relevant MeSH terms:
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Rifampin
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Respiratory Tract Infections
Lung Diseases
Respiratory Tract Diseases
Antibiotics, Antitubercular
 Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers