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

September 6, 2013 updated by: Radboud University Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic parameters of rifampicin, desacetylrifampicin, isoniazid, pyrazinamide, ethambutol
Time Frame: Steady state, week 6
Steady state, week 6

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

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

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

September 25, 2008

First Submitted That Met QC Criteria

September 25, 2008

First Posted (Estimate)

September 26, 2008

Study Record Updates

Last Update Posted (Estimate)

September 9, 2013

Last Update Submitted That Met QC Criteria

September 6, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APRIORI 4.1
  • PACTR2009060001493909 (Registry Identifier: www.pactr.org)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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