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.: PACTR202409710100607 Date of Registration: 02/09/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Therapeutic Drug Monitoring for antimicrobial agents for people living with HIV (TAP trial)
Official scientific title Therapeutic Drug Monitoring for antimicrobial agents for people living with HIV (TAP trial)
Brief summary describing the background and objectives of the trial Antimicrobial resistance (AMR) is a growing health concern, particularly in Africa, and is predicted to be the leading cause of death after cancer by 2050. Factors like overuse or inappropriate use of antibiotics, contribute to this crisis. People living with HIV (PLWH) are particularly vulnerable to AMR with potential drug-drug interactions between antiretroviral and antimicrobial agents against common organisms like Mycobacterium tuberculosis. There is limited data on the concentrations of commonly used antimicrobial agents in people living with HIV in resource-limited settings. Therapeutic Drug Monitoring (TDM) offers a promising approach to optimize antibiotic dosing and improve treatment outcomes for those with sub-optimal drug concentrations. TDM has been recommended for PLWH on anti-tuberculosis treatment due to sub-optimal drug concentrations found in a significant proportion of those with TB. Objectives: 1. To determine the concentrations of selected antimicrobial agents in people living with HIV requiring antimicrobial therapy. 2.To assess the utility of therapeutic drug monitoring in achieving therapeutic targets for people living with HIV receiving rifampicin and isoniazid for treatment of tuberculosis. 3.To develop and validate a population pharmacokinetic-pharmacodynamic model for use during therapeutic drug monitoring for selected antibiotics used among PLWH
Type of trial Non-Randomised
Acronym (If the trial has an acronym then please provide) TAP
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 02/09/2024
Actual trial start date
Anticipated date of last follow up 01/08/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 25
Actual target sample size (number of participants)
Recruitment status Not yet 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
Single Group Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Therapeutic Drug Monitoring of rifampicin and isoniazid We shall adjust the dose of isoniazid and rifampicin for participants found to have sub therapeutic drug levels of isoniazid and/or rifampicin at week 2 post initiation of TB treatment. Dose will be adjusted by adding an additional 75mg of isoniazid or 150mg of rifampicin at each TDM visit where applicable. 6 months Participants found with rifampicin and isoniazid concentrations below the reference ranges within the first 2 weeks of treatment will have their doses adjusted by an additional 75mg of isoniazid or 150mg of rifampicin by week 4. Drug levels will be measured again at week 6, and if still sub optimal, a further dose adjustment will be performed. Concentrations of intravenous ceftriaxone, oral amoxycillin, ciprofloxacin and azithromycin will be measured 2 hours post dosing (No intervention for those on antibiotics). 175 participants will be enrolled in the observation group. These will be on other antibiotics other than TB medications. 25
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Consenting PLWH aged 18 years and above 2. Patients being or who have been initiated on antibiotics which include; amoxicillin (+/- clavulanic acid), azithromycin, ciprofloxacin, rifampicin, isoniazid, ceftriaxone 3. Patients who are willing to and are able to comply with study procedures. 1. Patients who discontinue antibiotics for any reason following initiation 2. Patients receiving antibiotics only for prophylaxis Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 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 26/02/2024 Infectious Diseases Institute Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
P.O.box 22418 Upper Mulago Hill Road Kampala 256 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Pharmacokinetic parameters •Trough concentrations (Ctrough) or minimum concentrations (Cmin) defined as the lowest concentrations achieved prior to subsequent dosing •Maximum concentrations (Cmax) defined as the highest concentration achieved post dosing pharmacokinetic outcomes at 2, 4 and 6 weeks of TB treatment
Secondary Outcome Pharmacodynamic parameters •clinical response to treatment day 5-7 for those on antibiotics, 2, 4, 6 and 8 week and 6 months for those on TB treatment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Infectious Diseases Institute P.O.box 22418 Upper Mulago Hill Road Kampala Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Wellcome Trust through the CAMONET consortium 215 Euston Road, London, NW1 2BE. London NW1 2BE United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Infectious Diseases Institute P.O.box 22418 Upper Mulago Hill road Kampala Uganda Non Governmental Organization owned by a University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Christine Sekaggya csekaggya@idi.co.ug 256312307000 P.O Box 22418
City Postal code Country Position/Affiliation
Kampala Uganda Senior Research scientistPhysician
Role Name Email Phone Street address
Scientific Enquiries Christine Sekaggya csekaggya@idi.co.ug 256312307000 P.O.Box 22418
City Postal code Country Position/Affiliation
Kampala Uganda Senior Research Scientist and Physician
Role Name Email Phone Street address
Public Enquiries Hope Mackline hmackline@idi.co.ug 256312307000 P. O. Box 22418
City Postal code Country Position/Affiliation
Kampala Uganda Project Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Raw data that is de-identified will be available to other researchers. Study Protocol within 1-2 years following study completion Access to data will be given upon request to the Principle Investigator following signing of a data sharing agreement between both institutes. Access will be provided for both clinical and non-clinical data.
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