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.: PACTR2009040001261177 Date of Approval: 02/04/2009
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Optimization of tuberculosis and HIV co-treatment in Africa
Official scientific title Pharmacokinetic, pharmacogenetic aspects on drug-drug interactions between rifampicin and efavirenz
Brief summary describing the background and objectives of the trial Concomitant HIV and TB treatment is complicated due to interaction between rifampicin and efavirenz, cornerstones of anti-TB and HAART respectively. Rifampicin reduces plasma levels of efavirenz. Appropriate efavirenz dosage to be used with rifampicin is uncertain. The study aim to identify safe and effective HAART + TB treatment regimen and optimal efavirenz dose to be used with rifampicin.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) HIV TB Pharmagene
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: Drugs
Anticipated trial start date 09/01/2008
Actual trial start date
Anticipated date of last follow up 31/12/2012
Actual Last follow-up date
Anticipated target sample size (number of participants) 0
Actual target sample size (number of participants)
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 Non-randomised Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Non-randomised Open-label(Masking Not Used) Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Arm-2: HIV and Tuberculosis infected 600mg/day efavirenz + Rifampicine based TB therapy 48 weeks Efavirenz based HAART + Rifampicine based anti-tuberculosis treatmen 400
Control Group Arm-1:HIV but no Tuberculosis infected 600mg/day efavirenz 48 weeks Efavirenz based HAART 400 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion criteria for ARM-1 - HIV-infected patients > 18 years of age - Active TB excluded - CD4 cell count <200/mm3 or total lymphocyte counts (TLCs) below 1200/ mm3 at the time of TB diagnosis - Naïve to antiretroviral therapy and TB treatment - Adequate venous access and willingness to allow blood samples to be used for the studies - Ability to give informed consent and willingness to comply with study requirements and procedures. - Females of child-bearing potential who are able and willing to either practice abstinence or use consistent non-hormonal forms of birth control (such as condoms, diaphragms, IUDs, etc.) while taking efavirenz Inclusion criteria for ARM-2 - HIV-infected patients > 18 years of age and HAART to be initiated during TB treatment. - Newly diagnosed TB - CD4 cell count <200/mm3 or total lymphocyte counts (TLCs) below 1200/ mm3 at the time of TB diagnosis - Naïve to antiretroviral therapy and TB treatment - Adequate venous access and willingness to allow blood samples to be used for the studies - Ability to give informed consent and willingness to comply with study requirements and procedures. - A negative urine pregnancy test for females of child-bearing potential - Females of child-bearing potential who are able and willing to either practice abstinence or use of consistent non-hormonal forms of birth control (such as condoms, diaphragms, IUDs, etc.) while taking efavirenz Exclusion Criteria for ARM-1 - Haemoglobin < 8 gm/dL - Presence of persistent diarrhoea or malabsorption that would interfere with the subject's ability to absorb drugs. - Drug or alcohol abuse that may impair safety or adherence or interfere with the study results. - Positive pregnancy test or breastfeeding female. - Severely ill patients with Karnofsky score of < 40%.or patients receiving other medications that may have drug interaction with efavirenz. - Prisoners - Unable to give informed consent - Previously exposed to ART - Base line serum aminotransferase level raised 3 folds and above. Exclusion Criteria for ARM-2 - Haemoglobin < 8 gm/dL - Presence of persistent diarrhoea or malabsorption that would interfere with the subject's ability to absorb drugs. - Drug or alcohol abuse that may impair safety or adherence or interfere with the study results. - Positive pregnancy test or breastfeeding female. - Severely ill patients with Karnofsky score of < 40%.or patients receiving other medications that may have drug interaction with efavirenz. - Unable to give informed consent - Previously exposed to ART - Base line serum aminotransferase level raised 3 folds and above. - Prisoners 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 10/05/2007 1. Ethiopian National Ethics Committee, Ethiopian Science and Technology Agency, 2. Office of Research and publication, Muhimbili University Collage of health Sciences, Tanzania, 3. Stockholm regional ethics board, Sweden
Ethics Committee Address
Street address City Postal code Country
Addis Ababa P.O. Box 2490 Ethiopia
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 10/05/2007 1. Ethiopian National Ethics Committee, Ethiopian Science and Technology Agency, 2. Office of Research and publication, Muhimbili University Collage of health Sciences, Tanzania, 3. Stockholm regional ethics board, Sweden
Ethics Committee Address
Street address City Postal code Country
Addis Ababa P.O. Box 2490 Ethiopia
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 01/05/2007 Ethiopian Science and Technology Agency, National Health Research Ethics Review Committee, Addis Ababa University
Ethics Committee Address
Street address City Postal code Country
Feleke Kibret, PO Box 2490 Addis Ababa estc@ethionet.et Ethiopia
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 01/10/2006 STockholm Regional Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Anne Manninen, Box 289 Stockholm SE 171 77 Sweden
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 12/07/2007 Office of the Director of Research and Publications, Tanzania
Ethics Committee Address
Street address City Postal code Country
Prof. EE Kayaya, PO Box 65001 Dar Es Salaam drp@muchs.ac.tz Tanzania
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Secondary Outcome Safety of efavirenz based HAART; incidence of mortality, type, frequency and severity of adverse events such as CNS toxicity, rash and drug induced hepatotoxicity etc between patients in Arm-1 and Arm-2 Week 48 after initiation of efavirenz based HAART
Primary Outcome Efficacy of efavirenz based HAART as measured by plasma HIV-1 RNA load; proportion of patients with virologic success in patients in Arm-1 and Arm-2 Achieving a viral load of < 50 HIV-1 RNA copies/mL within 3¿6 months of starting therapy and then maintaining this thereafter
Secondary Outcome Efavirenz pharmacokinetic profile; proportion of patients with lower (<1 mg/l), normal therapeutic interval (1 to 4 mg/l) or higher (>4 mg/l) plasma efavirenz level in patients in Arm-1 and Arm-2. At week 4 and 16 after initiation of efavirenz based HAART
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Arada Health Center Addis Ababa Ethiopia
Muhimbili National Hospital Dar Es Salaam P.O. Box 65000 Tanzania
Infectious Disease Centre (IDC) Dar Es Salaam Tanzania
Mwananyamala District Hospital Dar Es Salaam Tanzania
Tikur Anbesa Hospital Addis Ababa P.O.Box 9086 Ethiopia
Beletschachew Health Center Addis Ababa Ethiopia
Kazanchis Health Center Addis Ababa Ethiopia
FUNDING SOURCES
Name of source Street address City Postal code Country
The European & Developing Countries Clinical Trials Partnership (EDCTP) Laan van Nieuw Oost Indië 300 The Hague P.O. Box 93015 Netherlands
The European & Developing Countries Clinical Trials Partnership (EDCTP) Laan van Nieuw Oost Indië 300 The Hague P.O. Box 93015 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Karolinska institutet Nobels väg 5, Solna Stockholm SE-171 77 Sweden University
Primary Sponsor Karolinska institutet Nobels väg 5, Solna Stockholm SE-171 77 Sweden University
COLLABORATORS
Name Street address City Postal code Country
Professor Ferdinand Mugusi, MD, PhD Department of Internal Medicine , Muhimbili University for Health and Allied Sciences Dar Es Salaam P.O. Box 65001 Tanzania
Professor Ferdinand Mugusi, MD, PhD Department of Internal Medicine , Muhimbili University for Health and Allied Sciences Dar Es Salaam P.O. Box 65001 Tanzania
Professor Eyasu Makonnen, B.Pharm, MSc, PhD Department of Pharmacology, Faculty of Medicine, Addis Ababa University, Addis Ababa University Addis Ababa P.O.Box 9086 Ethiopia
Professor Eyasu Makonnen, B.Pharm, MSc, PhD Department of Pharmacology, Faculty of Medicine, Addis Ababa University, Addis Ababa University Addis Ababa P.O.Box 9086 Ethiopia
Dr Mohamed Yakub Janabi, MD, PhD. Department of Internal Medicine , Muhimbili University for Health and Allied Sciences Dar Es Salaam P.O. Box 65001 Tanzania
Dr Mohamed Yakub Janabi, MD, PhD. Department of Internal Medicine , Muhimbili University for Health and Allied Sciences Dar Es Salaam P.O. Box 65001 Tanzania
Dr Omari Minzi, (B.Pharm, PhD) Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University for Health and Allied Sciences Dar Es Salaam P.O. Box 65013 Tanzania
Dr Omari Minzi, (B.Pharm, PhD) Department of Medicinal Chemistry, School of Pharmacy, Muhimbili University for Health and Allied Sciences Dar Es Salaam P.O. Box 65013 Tanzania
Dr. Collen Masimirembwa, PhD African Institute of Biomedical Science & Technology (AIBST) Harare P.O. Box. 2294 Zimbabwe
Dr. Collen Masimirembwa, PhD African Institute of Biomedical Science & Technology (AIBST) Harare P.O. Box. 2294 Zimbabwe
Dr Jürgen Burhenne, PhD Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, Im Neuenheimer Feld 410, University of Heidelberg Heidelberg D-69120 Germany
Dr Jürgen Burhenne, PhD Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, Im Neuenheimer Feld 410, University of Heidelberg Heidelberg D-69120 Germany
Professor Walter Emil Haefeli, MD, PhD Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, Im Neuenheimer Feld 410, University of Heidelberg Heidelberg D-69120 Germany
Professor Walter Emil Haefeli, MD, PhD Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, Im Neuenheimer Feld 410, University of Heidelberg Heidelberg D-69120 Germany
Professor Leif Bertilsson (PhD) Division of Clinical pharmacology Department of Laboratory Medicine, Karolinska University Hospital-Huddinge-C168, Karolinska Institutet Stockholm SE- 141 86 Sweden
Professor Leif Bertilsson (PhD) Division of Clinical pharmacology Department of Laboratory Medicine, Karolinska University Hospital-Huddinge-C168, Karolinska Institutet Stockholm SE- 141 86 Sweden
Professor Lars Linquist (MD, PhD.) Division of Infectious Diseases, Clinic for Infectious Diseases, Karolinska University Hospital I 63, Karolinska Institutet Stockholm SE 141 86 Sweden
Professor Lars Linquist (MD, PhD.) Division of Infectious Diseases, Clinic for Infectious Diseases, Karolinska University Hospital I 63, Karolinska Institutet Stockholm SE 141 86 Sweden
Professor Getachew Aderaye (MD, PhD.) Department of internal medicine, Faculty of Medicine, Addis Ababa University Addis Ababa P.O. Box 9086 Ethiopia
Professor Getachew Aderaye (MD, PhD.) Department of internal medicine, Faculty of Medicine, Addis Ababa University Addis Ababa P.O. Box 9086 Ethiopia
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Eleni Aklillu Eleni.aklillu@ki.se +46 73 511 61 31 - Karolinska University Hospital-Huddinge-C168
City Postal code Country Position/Affiliation
Stockholm SE- 141 86 Sweden Division of Clinical pharmacology Department of Laboratory Medicine, Karolinska Institutet
Role Name Email Phone Street address
Public Enquiries Leif Bertilsson Leif.bertilsson@ki.se +46 8 5858 1071 - Karolinska University Hospital-Huddinge-C168
City Postal code Country Position/Affiliation
Stockholm SE- 141 86 Sweden Division of Clinical pharmacology Department of Laboratory Medicine, Karolinska Institutet
Role Name Email Phone Street address
Scientific Enquiries Eleni Aklillu Eleni.aklillu@ki.se + 46 73 511 6131 - Karolinska University Hospital-Huddinge-C168
City Postal code Country Position/Affiliation
Stockholm SE- 141 86 Sweden Division of Clinical pharmacology Department of Laboratory Medicine, Karolinska Institutet
REPORTING
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