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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR2010030001971409 Date of Registration: 08/03/2010
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Pharmacokinetic study: interactions b/w Artemisinin-based Combination and Antiretroviral therapies in Malawi Phase I Step 2
Official scientific title Special populations and label explansion studies with the fixed does combinations artemether-lumefantrine, amodiaquine-artesunate, and dihydroartemisinin-piperaquine in Zambia, Malawi and Mozambique
Brief summary describing the background and objectives of the trial HIV-infected people receiving antiretroviral drugs (ARVs) living in malaria-endemic areas will become infected with malaria and will need treatment with Artemisinin-based Combination Therapies (ACTs). In this first phase of our study, we will assess the pharmacokinetics and safety of ACTs when administered to malaria uninfected people receiving ARVs. Once safety has been proved, we will conduct a second phase of the study to assess efficacy of ACTs in curing malaria in people taking ARVs.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) ADAPT Project
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS,Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 03/10/2011
Actual trial start date 02/01/2012
Anticipated date of last follow up 14/01/2013
Actual Last follow-up date
Anticipated target sample size (number of participants) 155
Actual target sample size (number of participants) 162
Recruitment status Completed
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)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group 3TC-AZT-TDF-LPV/r plus AL 3TC (150mg) -AZT (300mg) twice daily plus Tenofovir (TDF; 300mg) once daily plus Lopinavir (200mg)/ritonavir (50mg) 2 tablets twice daily plus 4 tablets artemether/lumefantrine (20/120mg) twice da 3 days Second Line ARVs plus AL 15
Control Group AL (without any ARVs) 4 tablets artemether/lumefantrine (20/120mg) twice daily 3 days artemether/lumefantrine without any ARVs 10 Dose Comparison
Experimental Group 3TC -d4T-EFV plus AL 3TC (150mg) - d4T (30mg) twice daily plus Efavirenz (EFV; 600mg) once daily plus 4 tablets artemether/lumefantrine (20/120mg) twice daily 3 days Alternative first line ARV plus AL 15
Experimental Group 3TC -d4T-NVP plus AQ-AS 3TC (150mg) -d4T (30mg)-NVP (200mg) twice daily plus 2 tablets artesunate/amodiaquine (100mg/270mg) once daily 3 days First line ARVs plus AQ-AS 25
Experimental Group 3TC-AZT-TDF-LPV/r plus AQ-AS 3TC (150mg) -AZT (300mg) twice daily plus Tenofovir (TDF; 300mg) once daily plus Lopinavir (200mg)/ritonavir (50mg) 2 tablets twice daily plus 2 tablets artesunate/amodiaquine (100mg/270mg) once daily 3 days Alternative first line ARV plus AQ-AS 25
Control Group AQ-AS 2 tablets artesunate/amodiaquine (100mg/270mg) once daily 3 days Artesunate/amodiaquine without any ARVs 25 Dose Comparison
Experimental Group 3TC -d4T-EFV plus DHA-PQ 3TC (150mg); d4T (30mg) twice daily plus Efavirenz (EFV; 600mg) once daily plus 4 tablets dihydroartemisinin/piperaquine (40mg/320mg) once daily 3 days Alternative first line ARV plus DHA-PQ 15
Experimental Group 3TC -d4T-NVP plus DHA-PQ 3TC (150mg)-d4T (30mg)-NVP (200mg) twice per day plus 4 tablets dihydroartemisinin/piperaquine (40mg/320mg) once daily 3 days First line ARVs plus DHA-PQ 15
Control Group DHA-PQ without any ARVs 4 tablets dihydroartemisinin/piperaquine (40mg/320mg) once daily 3 days dihydroartemisinin/piperaquine without any ARVs 10 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Residence of Blantyre City and the neighbouring districts. 2. Confirmed HIV positive clients a. ART naïve: with CD4 Cell count ¿350 cells/mm3 b. ART-treated: with CD4 cell count ¿250 cells/mm3 and receiving first-line, alternative first line or second line ART, as described in the background section, for ¿6 months. 3. Age ¿18 years 4. Ability to read and write and provide informed consent 5. Body weight at least 40kgs (so that they are eligible to receive recommended adult doses of the antimalarial drug) 6. Stated willingness to be contacted by phone or at home. 7. Stated willingness to be admitted in the hospital for 3 days and to remain within the vicinity of Blantyre city for 2 months after enrolment. 1. Body Mass Index less than 18.5kg/m2 2. CD4 Cell count <350 cells/mm3 among antiretroviral naïve subjects and CD4 Cell count <250 cells/mm3 among ART-treated subjects. 3. Hemoglobin <8.5 g/dL 4. Receiving any antimalarial drugs within the past 4 weeks. 5. Receiving other drugs which are known inhibitors or inducers of P450 enzymes of P-glycoprotein (except cotrimoxazole prophylaxis, which is the standard of care in HIV-infected people). 6. History of regular intake of alcohol (>twice/week), tobacco (>3 times/week) or any use of illicit drugs 7. History or evidence of pre-existing diseases of the liver and kidneys ie if the serum transaminases levels are >3 times the upper limit of normal or urea and creatinine levels >1.5 times the upper limit of normal. 8. History or evidence of heart disease, including conductive abnormalities on electrocardiographs (ECGs) ie QTc interval>450ms (men) and >470ms (females) 9. Clinical and/or laboratory evidence of other infections in addition to HIV, such as clinical malaria or microscopic asexual forms of Pf malaria, hepatitis B, pneumonia, tuberculosis, bacteremia etc. 10. Laboratory evidence of potentially life threatening white blood cell disorders such as neutropenia (absolute neutrophil count < 0.500*109), lymphopenia (absolute lymphocyte count <0.35*109) and thrombocytopenia (absolute platelet count <25*109). 11. Physically unfit with Karnofsky score of <80%. 12. Hypersensitivity to any of the ACTs. 13. Pregnancy ie confirmed by a Human Chorionic Gonadotrophin test. 14. Current participation in any other therapeutic or vaccine trial 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 04/08/2009 Malawi College of Medicine Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Mahatma Gandhi Road, Mahatma Gandhi Campus Blantyre Bt3 Malawi
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 13/01/2010 LIverpool School Of Tropical Medicine (LSTM) Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Pembroke Place Liverpool L35QA United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Area under the curve (AUC) for the ACT AUC computed from a concentration-time curve
Primary Outcome adverse events At anytime from administration of ACT to 28 days post dosing.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Queen Elizabeth Central Hospital Chipatala Ave Blantyre Bt3 Malawi
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP 344 Laan van Nieur Oost Indie The Hauge 2593 CE Netherlands
EDCTP 344 Laan van Nieur Oost Indie The Hauge 2593 CE Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Liverpool School of Tropical Medicine Pembroke Place Liverpool L35QA United Kingdom University
Primary Sponsor Liverpool School of Tropical Medicine Pembroke Place Liverpool L35QA United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Instituut voor Tropische Geneeskunde Nationalestraat 155 Antwerp B2000 Belgium
Instituut voor Tropische Geneeskunde Nationalestraat 155 Antwerp B2000 Belgium
Vienna School of Clinical Research Kolblgasse 10 Vienna 1030 Austria
Vienna School of Clinical Research Kolblgasse 10 Vienna 1030 Austria
College of Medicine Research Support Center Mahatma Gandhi Road Blantyre Bt3 Malawi
College of Medicine Research Support Center Mahatma Gandhi Road Blantyre Bt3 Malawi
Malawi-Liverpool Wellcome Trust Clinical Research Programme (MLW) Chipatala Ave Blantyre Bt3 Malawi
Malawi-Liverpool Wellcome Trust Clinical Research Programme (MLW) Chipatala Ave Blantyre Bt3 Malawi
Centro de Investigacao em Saude da Manhica (CISM) None Manhica None Mozambique
Centro de Investigacao em Saude da Manhica (CISM) None Manhica None Mozambique
Tropical Disease Research Centre Sixth Floor of Ndola Cental Hospital Ndola 101010 Zambia
Tropical Disease Research Centre Sixth Floor of Ndola Cental Hospital Ndola 101010 Zambia
Fundacio Privada Clinic per la Recerca Biomedica c/ Villaroel 170 Barcelona 08036 Spain
Fundacio Privada Clinic per la Recerca Biomedica c/ Villaroel 170 Barcelona 08036 Spain
Liverpool School of Tropical Medicine Pembroke Place Liverpool L35QA United Kingdom
Liverpool School of Tropical Medicine Pembroke Place Liverpool L35QA United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Victor Mwapasa vmwapasa@medcol.mw +265 1 876 444 Chipatala Ave (PO Box 30096, Chichiri)
City Postal code Country Position/Affiliation
Blantyre Bt3 Malawi Associate Professor/Malawi-Liverpool Wellcome Clinical Research Programme
Role Name Email Phone Street address
Public Enquiries Dianne Terlouw d.j.terlouw@liv.ac.uk +44 151 7053354 Pembroke PLace
City Postal code Country Position/Affiliation
Liverpool L3 5QA United Kingdom
Role Name Email Phone Street address
Scientific Enquiries Victor Mwapasa vmwapasa@medcol.mw +265 1 876 444 Chipatala Ave (PO Box 30096, Chichiri)
City Postal code Country Position/Affiliation
Blantyre Bt3 Malawi Associate Professor/Malawi-Liverpool Wellcome Clinical Research Programme
REPORTING
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