Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR2009060001493909 Date of Approval: 19/06/2009
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title High RIF
Official scientific title Pharmacokinetics and -dynamics of high versus standard dose rifampicin in patients with pulmonary tuberculosis in the Kilimanjaro Region, Tanzania
Brief summary describing the background and objectives of the trial The current tuberculosis (TB) treatment is lengthy and complex, resulting in problems of nonadherence, inadequate treatment response and resistance development. Shortening the duration of TB treatment will help solving these problems. Increasing the dose of rifampicin in standard TB treatment is expected to reduce treatment duration. This study will focus on the pharmacokinetics and -dynamics of higher than standard doses of rifampicin in first-line TB treatment.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) High RIF
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/09/2009
Actual trial start date 13/08/2010
Anticipated date of last follow up 31/01/2012
Actual Last follow-up date 31/01/2012
Anticipated target sample size (number of participants) 150
Actual target sample size (number of participants)
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
NCT00760149 ClinicialTrials.gov
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Blocked randomization (block size: 6), after stratification for gender and HIV-status Sealed opaque envelopes Masking/blinding used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Blocked randomization (block size: 6), after stratification for gender and HIV-status Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Higher dose rifampicin(900 mg) Rifampicin 900 mg; isoniazid 300 mg; pyrazinamide 30 mg/kg; ethambutol 15 mg/kg; 1 placebo tablet for rifampicin 300 mg. 2 months Higher than standard dose rifampicin (900 mg) in otherwise standard intensive phase TB treatment 50
Experimental Group Higher dose rifampicin (1200 mg) Rifampicin 1200 mg; isoniazid 300 mg; pyrazinamide 30 mg/kg; ethambutol 15 mg/kg. 2 months Higher than standard dose rifampicin (1200 mg) in otherwise standard intensive phase TB treatment 50
Control Group Standard, first-line TB treatment during intensive phase of TB treatment Rifampicin 600 mg; isoniazid 300 mg; pyrazinamide 30 mg/kg; ethambutol 15 mg/kg; 2 placebo tablets for rifampicin 300 mg. 2 months No intervention for the control group (except for two placebo tablets in addition to the standard TB treatment regimen). 50 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Participant has newly diagnosed pulmonary tuberculosis, confirmed by a positive smear of at least two spontaneously produced sputum samples with ZN staining. 2. Participant is willing to be tested for HIV. 3. Participant is at least 18, but no more than 65 years of age at the day of the first dosing of study medication. 4. Participant is admitted to Kibong'oto National Tuberculosis Hospital (KNTH) or Kilimanjaro Christian Medical Centre (KCMC) during the intensive phase of TB treatment. 5. Participant is able and willing to attend to KNTH or KCMC regularly during the continuation phase of TB treatment. 6. Participant is able to understand and willing to sign the Informed Consent Form prior to screening evaluations. 1. Participant has been treated with anti-tuberculosis drugs during the past three years. 2. Participant's body weight is less than 50 kg. 3. Participant has abnormal liver function test or creatinine (defined as levels higher than the upper limit of normal). 4. Participant has a relevant 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). 5. Participant is on anti-retroviral treatment at inclusion. 6. Participant has a CD4 count less than 350 cells/mm3 7. Participant has a Karnovsky score of less than 40. 8. Participant is pregnant or breastfeeding. 9. Participant is using immunosuppressive drugs, such as steroids or cyclofosfamides. 10. Participant has a rifampin resistant or Multi Drug Resistant (MDR-) TB for which another than the standard regimen is needed. 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/12/2007 KCMC Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
KCMC Moshi 2240 United Republic of Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/08/2008 National Institute for Medical Research
Ethics Committee Address
Street address City Postal code Country
NIMR Dar es Salaam 9653 United Republic of Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 24/03/2009 Tanzanian Food and Drug Authority
Ethics Committee Address
Street address City Postal code Country
Nelson Mandela Road Dar es Salaam 77150 United Republic of Tanzania
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Pharmacokinetics of rifampicin 24h Pharmacokinetics curve at steady state; week 3 after start of treatment.
Primary Outcome Occurrence of adverse events Week 0, 1, 2, 4, 6, 8, 10 and 12 after start of treatment
Primary Outcome Short-term bacteriological response (sputum culture conversion and Serial Sputum Colony Forming Units Count, SSCC) Week 0, 1, 2, 3, 4, 5, 6, 7, 8
Secondary Outcome Accuracy of surrogate markers (SSCC, mRNA, cytokines) Week 0, 1, 2, 3, 4, 5, 6, 7, 8
Secondary Outcome Occurrence of mixed Mycobacterium tuberculosis strain infections Week 0
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kibong'oto National Tuberculosis Centre (KNTH) Kibong'oto Sanya Juu 12 United Republic of Tanzania
Kilimanjaro Christian Medical Centre (KCMC) KCMC Moshi 3010 United Republic of Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
European & Developing Countries Clinical Trials Partnership (EDCTP) Laan van Nieuw Oost Indië 334 The Hague Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor African Poverty Related Infection Oriented Research Initiative (APRIORI) Radboud Nijmegen Medical Centre Nijmegen 9101, 6500 HB Netherlands University
Primary Sponsor African Poverty Related Infection Oriented Research Initiative (APRIORI) Radboud Nijmegen Medical Centre Nijmegen 9101, 6500 HB Netherlands University
Primary Sponsor Prof. Dr. D.M. Burger Radboud University Nijmegen Medical Centre, Geert Grooteplein 10 Nijmegen 6525 GA Netherlands University
Secondary Sponsor Dr. M.J. Boeree University Centre for Chronic Diseases Dekkerswald, Nijmeegsebaan 31 Groesbeek 6561 KE Netherlands University
Secondary Sponsor Dr. R.E. Aarnoutse Radboud University Nijmegen Medical Centre, Geert Grooteplein 10 Nijmegen 6525 GA Netherlands University
COLLABORATORS
Name Street address City Postal code Country
Kilimanjaro Christian Medical Centre (KCMC) KCMC Moshi 3010 United Republic of Tanzania
Kilimanjaro Christian Medical Centre (KCMC) KCMC Moshi 3010 United Republic of Tanzania
Kibong'oto National Tuberculosis Hospital (KNTH) Kibong'oto Sanya Juu 12 United Republic of Tanzania
Kibong'oto National Tuberculosis Hospital (KNTH) Kibong'oto Sanya Juu 12 United Republic of Tanzania
Radboud University Nijmegen Medical Centre Geert Grooteplein 8 Nijmegen 6525 GA Netherlands
Radboud University Nijmegen Medical Centre Geert Grooteplein 8 Nijmegen 6525 GA Netherlands
University Centre for Chronic Diseases Dekkerwald Nijmeegsebaan 31 Groesbeek 6561 KE Netherlands
RIVM, National Institute for Public Health and the Environment Bilthoven 3720 BA Netherlands
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Rob Aarnoutse r.aarnoutse@akf.umcn.nl +31 24 3616405 Geert Grooteplein 10
City Postal code Country Position/Affiliation
Nijmegen 9101, 6500 HB Netherlands Department of Clinical Pharmacy, pharmacist
Role Name Email Phone Street address
Public Enquiries Martin Boeree m.boeree@ulc.umcn.nl +31 24 6859297 Nijmeegsebaan 31
City Postal code Country Position/Affiliation
Groesbeek 66, 6560 AB Netherlands Respiratory medicine physician, medical director University Lung Centre Dekkerswald
Role Name Email Phone Street address
Scientific Enquiries Gibson Kibiki gkibiki@gmail.com +255 754 572767 KCMC
City Postal code Country Position/Affiliation
Moshi 3010 United Republic of Tanzania Internal medicine physician
REPORTING
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