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.: PACTR202105618971235 Date of Approval: 05/05/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Clinical validation of a CYP2B6 pharmacogenetics test and dosing algorithm in the safe and efficacious use of Efavirenz and its cost effective & benefit analysis in a public healthcare setting
Official scientific title Clinical validation of a CYP2B6 pharmacogenetics test and dosing algorithm in the safe and efficacious use of Efavirenz and its cost effective & benefit analysis in a public healthcare setting
Brief summary describing the background and objectives of the trial Early observations of huge inter individual variation in the exposure levels of Efavirenz (EFV) in patients led to the discovery of a genetic variation in the liver enzyme (CYP2D6) responsible for the metabolism and elimination of EFV in some patients. these patients had high levels of the drugs and were prone to severe EFV associated adverse drug reactions (ADRs) including depression, headaches, suicidality and nightmares among other neuropsychiatric side effects.Clinical observation in Europe showed that people of African origin were more susceptible to the neuropsychiatric effects of EFV than Caucasian populations. The high prevalence of the CYP2B6*6 positively corerealted with neuropsychiatric adverse drug reactions in Zimbabwe with 30% of patients on EFV reporting severe adverse drug reactions. the database for adverse drug reactions reporting shows EFV as the second highest cause of reported ADRs in Africa, after Nevirapine (NVP) making it a public health problem of enormous proportions. Primary Objectives: - to establish the non-inferiority of the CYP2B6 genetic test guided dosing of EFV against the standard dose of 400mg/day with respect to treatment efficacy - To establish the superiority of the CYP2B6 genetic test guided dosing of EFV over the standard dose of 400mg/ day with respect to potential reduction of neuropsychiatric side effects. Secondary Objectives: - To determine the cost effectiveness and benefits of using the CYP2B6 genotype guided dosing of EFV against the standard dose of 400mg/day in a public healthcare setting.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) EFV
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 02/04/2018
Actual trial start date 05/10/2018
Anticipated date of last follow up 01/04/2018
Actual Last follow-up date 03/12/2019
Anticipated target sample size (number of participants) 260
Actual target sample size (number of participants) 241
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
CT1472017 Medicines Control Authority of Zimbabwe
A2144 Medical Research Council of Zimbabwe
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 Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Efavirenz 400mg 5 weeks Efavirenz based regimen 400mg 200
Control Group Efavirenz 200mg 96 weeks Efaviren 60 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. HIV infected adults between 18 and 50 years 2. CD4 T-cell counts between 50-500 cells per ul 3. No previous AIDS defining illness 4. Plasma HIV-1 RNA of at least 1000 copies per ml 5. No short course for preventing mother to child transmission 6. No previous exposure to antiretroviral therapy 1. Pregnancy or nursing mothers 2. Had uncontrolled active opportunistic or malignant disease 3. Present or recent use of prohibited or elicit medications adversely affecting participation 4. Laboratory values outside predefined ranges - i. Absolute neutrophil count <500 celss per ul ii. Haemoglobin <7.0 g/dl iii. Platelet count <50 000 cells per ul iv. Aspartate aminotransferase, or alanine aminotransferase, or both >5 times the upper limit normal Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 50 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 04/04/2017 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Mazowe Street Harare 00000 Zimbabwe
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. viral load as a measure of regimen efficacy. This will be determined by qRT-PCR 2. Incidences and severity of neuropsychiatric adverse drug reactions this will be determined by neuropsychiatric adverse effects evaluation tools 1, 2, 3, 4, 5 weeks
Secondary Outcome Efavirenz plasma concentrations and correlations with CYP2B6 genotype and relation to neuropsychiatric side effects. The EFV concentrations will be determined by LC-MSMS and the CYP2B6 genotype by the QRTPCR method, which will have been validated in this study. 1, 2, 3, 4, 5 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Chitungwiza Central Hospital Batani Street Zengeza 4 Chitungwiza Chitungwiza 00000 Zimbabwe
Zengeza Clinic Zengeza Chitungwiza 0000 Zimbabwe
St Marys Clinic St Marys Chitungwiza 0000000 Zimbabwe
Seke South Clinic Seke Chitungwiza 0000 Zimbabwe
Seke North Clinic Seke North Chitungwiza 0000 Zimbabwe
FUNDING SOURCES
Name of source Street address City Postal code Country
Sanbio Office 48 Meiring Naude Road Brummeria Pretoria 0001 South Africa Pretoria 001 South Africa
Germany Health Protection Program Jens Spahn, Bon Office RochusstraBe Rouchusstrabe Germany
EDCTP FranceVan Ziji Drive Cape town South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor African Institute of Biomedical Science and Technology Wilkins Hospital Cnr Proncess and J, Tongogara Road Harare 0000 Zimbabwe Funding Agency
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Collen Masimirembwa collenmasimirembwa@yahoo.com +263772422951 Wilkins Hospital Cnr Princes and J. Tongogara
City Postal code Country Position/Affiliation
Harare 0000 Zimbabwe Chief Scientific Officer
Role Name Email Phone Street address
Scientific Enquiries Justen Manasa jmanasa@aibst.edu.zw +263774633549 Wilkins Hospital Cnr Princes and J. Tongogara
City Postal code Country Position/Affiliation
Harare 0000 Zimbabwe Laboratory Manager
Role Name Email Phone Street address
Public Enquiries Roslyn Thelingwani rthelingwani@aibst.edu.zw +263773817401 Wilkins Hospital Cnr Princes and J. Tongogara
City Postal code Country Position/Affiliation
Harare 0000 Zimbabwe Pharmacologist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) Clinical Study Report Beginning 9 months and ending 36 months following article publication Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. This will be towards achieving aims of the approved proposal
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information