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.: PACTR201310000629390 Date of Approval: 24/08/2013
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Rifabutin with lopinavir/ritonavir in patients coinfected with tuberculosis and HIV in Burkina Faso
Official scientific title Rifabutin with lopinavir/ritonavir in patients coinfected with tuberculosis and HIV in Burkina Faso
Brief summary describing the background and objectives of the trial Rifamycin (Rifampicin or Rifabutin) is the principal molecule of conventional TB treatment regimens, including people living with HIV co-infected by TB, but the clinical management of cases of tuberculosis and HIV co-infection is made difficult by several factors, including the important drug interactions between the rifamycins (rifampin and rifabutin) and antiretroviral drugs of the class of protease inhibitors (PI). The basis of the interaction lies in the induction by rifamycins of liver microsomal cytochrome P450-related in particular to its CYP3A4 isoform through which is the hepatic metabolism of IP which, overall, decreased blood concentrations. For this reason, rifampicin can not be used in association with IP, and rifabutin, which has a much more modest inducing effect, is the anti-tuberculosis drug of choice in this clinical situation. This clinical study aims to determine the pharmacokinetics parameters of RFB in combination with Lopinavir/ritonavir in Burkinabe HIV infected patients with tuberculosis, in order, to define optimal doses that will be further tested in a larger phase III trial comparing safety, tolerability and efficacy of RBT and RMP regimens in West Africa.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) RIFLOPI
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS,Tuberculosis
Purpose of the trial Treatment: Other
Anticipated trial start date 28/11/2013
Actual trial start date
Anticipated date of last follow up 31/12/2015
Actual Last follow-up date
Anticipated target sample size (number of participants) 30
Actual target sample size (number of participants) 0
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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
Parallel: different groups receive different interventions at same time during study Randomised simple randomisation using a radomisation table created by a computer sofware program allocation was determined by the holder of sequence who is situation off site Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised simple randomisation using a radomisation table created by a computer sofware program allocation was determined by the holder of sequence who is situation off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Rifabutin 150 mg Rifabutin (Mycobutin ®) 150mg every other day + standard regimen of treatment +Lopinavir / ritonavir (Kaletra ®) 200/50 mg X 2 associated with 2 NRTIs 6 months The tablets of rifabutin (150 mg) should be taken in the morning at 7 am, on alternate days one hour before the breakfast. The tablets of lopinavir / ritonavir should be taken in the morning at 8 (cps two 200/50 mg) and in the evening at 8 pm (two 200/50 mg cps), regardless of meals. 15
Control Group control group Rifabutin (Mycobutin ®) 150mgx2 every other day + standard regimen of treatment+Lopinavir / ritonavir (Kaletra ®) 200/50 mg X 2 associated with 2 NRTIs 6 months The tablets of rifabutin (150 mg) should be taken in the morning at 7 am, on alternate days one hour before the breakfast. The tablets of lopinavir / ritonavir should be taken in the morning at 8 (cps two 200/50 mg) and in the evening at 8 pm (two 200/50 mg cps), regardless of meals 15 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- HIV-1 infected patient - Patient aged ¿18 years(minimum) and ¿ 60 years (maximum) - Eligible for antiretroviral therapy including Lopinavir/ritonavir regimen (national guideline) - Any CD4+ - New pulmonary tuberculosis (TPM), confirmed or suspected - Eligible for antimycobacterial therapy including rifabutin - Signed informed consent form - For female patients : pregnancy test negative, non lactating, not planning to become pregnant during the follow-up period of the study. - Patient doubly infected HIV 1 and 2 or HIV2 - ALAT > 5 NV - creatinine> 3 NV - Co-administration of treatment with an absolute contre indication (list to be established)Pregnancy or breastfeeding - Presence of medical conditions or other conditions (allergy, intolerance) that contraindicate the administration of a drug in the studioChoice of the clinician to take antiretroviral therapy other than as provided under the Protocol - People with MDR or XDR tuberculosis strain from - Any medical condition that in the opinion of the investigator poses a risk to the patient 18 Year(s) 60 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 02/05/2012 National ethic committee
Ethics Committee Address
Street address City Postal code Country
Ouagadougou 03 BP 7009 Burkina Faso
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Area under the curve of rifabutin and the area under curve of Lopinavir/ritonavir : - Measured after 15 days of combined treatment rifabutin - lopinavir/ritonavir 15 days: area under the curve pharmacokinetics (AUC) of Rifabutine 150 mg, Rifabutine 300 mg and Lopinavir/Ritonavir: Variation of Cmax between the two doses of rifabutin: 15 days, - Correlation between plasma levels of rifabutin and outcomes of antimycobacterial therapy: 15 days, 1, 2,3,4,5,6 months
Secondary Outcome The number of subjects with adverse events to the development of combination treatment (both rifabutin that Lopinavir /r) during treatment with rifabutin 150 mg or 300 mg. - Frequency of adverse events associated with combination treatment and correlation with levels of lopinavir Cmin ever
Secondary Outcome The number of subjects with adverse events to the development of combination treatment (both rifabutin that Lopinavir /r) during treatment with rifabutin 150 mg or 300 mg. - Frequency of adverse events associated with combination treatment and correlation with levels of lopinavir Cmin ever
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
CDT du CMA de Pissy AVENUE DU PROGRES, PORTE 209 Ouagadougou Burkina Faso
CMA du secteur 30 AVENUE DES TANSOABA, porte 1929 Ouagadougou Burkina Faso
CDTdu CMA de Kossodo Rue Kend Noom, 282 Ouagadougou Burkina Faso
CNLAT AVENUE KUMDA YOONRE, porte 310 Ouagadougou Burkina Faso
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP 334 Laan van Nieuw Oost Indië, 2593 CE The Hague P.O. Box 93015, 250 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Institut de Recherche en Santé (IRSS) Rue 29.09 porte 35 Ouagadougou 03 BP 7192 Burkina Faso University
COLLABORATORS
Name Street address City Postal code Country
Henri Gautier Ouedraogo Rue 29.09 porte 35 Ouagadougou 03 BP 7192 Burkina Faso
Alberto MATTEELLI Piazza Spedali Civili, 1 25100 Brescia Brescia Italy
Isidore Moyenga AVENUE KUMDA YOONRE, porte 310 Ouagadougou 01 BP 6632 Burkina Faso
REGAZZI Marrio Piazzale Golgi 2, 27100 Pavia Laboratory of Clinical Pharmacokinetics IRCSS Foundation Policlinico San Matteo di Pavia Italy
Alberto Roggi AVENUE KUMDA YOONRE, porte 310 Ouagadougou 01 BP 6632 Burkina Faso
Serges Diagbouga Rue 29.09 porte 35 Ouagadougou 03 BP 7192 Burkina Faso
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Seni Kouanda skouanda@irss.bf +226 50335684 Rue 29.09 porte 35
City Postal code Country Position/Affiliation
Ouagadougou 03 BP 7192 Burkina Faso Head of biomedical and public health department at IRSS
Role Name Email Phone Street address
Public Enquiries Henri Gautier Ouedraogo gouedraogo@irss.bf +226 50335684 Rue 29.09 porte 35
City Postal code Country Position/Affiliation
Ouagadougou 03 BP 7192 Italy PharmD, MSC, research assistant
Role Name Email Phone Street address
Scientific Enquiries Alberto Matteelli matteelli@med.unibs.it +39.030.3995671 Rue 29.09 Porte 35
City Postal code Country Position/Affiliation
Brescia Italy Institute of Infectious and Tropical Diseases,
REPORTING
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Result URL Hyperlinks
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