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.: PACTR202006835180506 Date of Approval: 17/06/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A5381
Official scientific title Observational Cohort To Assess Therapeutic Efficacy And Emergence Of HIV Drug Resistance Following Initiation Of Tenofovir-Lamivudine-Dolutegravir (TLD) For First- Or Second-Line ART
Brief summary describing the background and objectives of the trial This is a study for people who have HIV and qualify to switch to or receive Dolutegravir containing antiretroviral therapy (ART, group of medicine used to treat HIV). Taking TLD (combination pill of three medicines for HIV, tenofovir-lamivudine-dolutegravir) has shown to be better tolerated, work better against the virus known as virologic efficacy, have fewer drug-drug interactions, and have less frequent onset of HIV drug resistance than Efavirenz containing ART. Rationale There is limited data on the performance and emergence of resistance to TLD in diverse settings. Understanding the risks and benefits of TLD rollout is a priority research question, as many programs in low- and middle-income countries (LMIC) may not use viral load testing in the transition to DTG-based, first-line ART and will not have the benefit of individual resistance testing to guide ART optimization
Type of trial CCT
Acronym (If the trial has an acronym then please provide)
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 01/07/2020
Actual trial start date
Anticipated date of last follow up 30/09/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 100
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
3910 kenya Medical Research Institute Scientific and Ethical Review Unit
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
Crossover: all participants receive all interventions in different sequence 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 Group 1 36 months Participants switching to TLD, after taking prior anti-HIV medication that contains a NNRTI drug (a group of medicines scientifically known as non-nucleoside reverse transcriptase inhibitors, such as Efavirenz or Nevirapine). 25
Experimental Group Group 2 36 months Participants switching to TLD, after taking anti-HIV medication that contains a PI drug (a group of medicines scientifically known as protease inhibitors, such as Lopinavir or Atazanavir). 25
Experimental Group Group 3 36 months Participants taking TLD and receiving medication for TB (tuberculosis) that includes the drug rifampicin. These participants must be starting one or both of these medications when they enter the study. 25
Experimental Group Group 4 36 Months Participants starting TLD who have not taken anti-HIV medication before. 25
Control Group There is no Control group N/A N/A 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion Criteria 1.Receiving care at a PEPFAR-supported site. 2 Documentation of HIV-1 infection acceptable to the local PEPFAR-supported program to allow antiretroviral (ARV) treatment to be initiated or continued. 3 Age more than or equal to 10 years. 4 Ability and willingness of participant or legal guardian/representative to provide informed consent to participate in the study. 5 Expectation that the participant will receive care within the local PEPFARsupported program and will be able to be followed for study evaluations for at least 6 months and ideally for 36 months. Exclusion Criteria 1. Weight less than 30 kg. 2 For participants already on ART in Groups 1, 2, and 3, known to have had an ART interruption encompassing the entire 14 day window (≥14 consecutive days) immediately prior to study entry. 3 For Group 3, if a participant is already taking TLD at the time of study entry, HIV- 1 RNA >1000 copies/mL within the past 9 months while taking TLD with no subsequent HIV-1 RNA ≤1000 copies/mL. 4 Prior enrollment in any group in this study. 5 For Group 3 participants, already on concomitant TLD and RIF-containing TB treatment prior to study entry. Adolescent: 13 Year-18 Year 10 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 17/09/2019 KEMRI scientifics and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Kemri .Mbagathi way, Nairobi PO BOX 54840 Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Primary Outcome Measures For Groups 1, 2, and 4: Virologic success, defined as suppression of plasma HIV-1 RNA to ≤1000 copies/mL, at 6 months after starting TLD. This will be based on the measurement closest to exactly 6 months (i.e., 183 days) after the date of start of TLD, within the window of 6 months ±3 months (specifically 92 to 274 days, inclusive). For participants experiencing virologic failure (HIV-1 RNA >1000 copies/mL) at 6 months after starting TLD, new DTG resistance mutations defined as those present at the time of virologic failure confirmation that were not present at the time of starting TLD. For Group 3: Virologic success, defined as suppression of plasma HIV-1 RNA to ≤1000 copies/mL, at the end of concomitant TLD (including an additional daily dose of DTG 50 mg such that DTG is taken twice daily) and RIF-containing TB treatment. This will be the measurement closest to the end of concomitant treatment within the window of 4 weeks (28 days) before the end to 6 months (183 days) after the end, inclusive. For participants experiencing virologic failure (HIV-1 RNA >1000 copies/mL) at the end of concomitant TLD (including an additional daily dose of DTG 50 mg such that DTG is taken twice daily) and RIF-containing TB treatment, new DTG resistance mutations defined as those present at the time of the virologic failure confirmation thatwere not present at the time of starting TLD. 6 months
Secondary Outcome 1. Treatment outcome measure based on the FDA Snapshot algorithm at 6 months, 12 months, 24 months, and 36 months after starting TLD in each of Groups, 1a, 1b, 2a, 2b, and 4; and at the end of concomitant TLD and RIF-containing TB treatment, 12 months, 24 months, and 36 months after starting concomitant TLD and RIFcontaining TB treatment in Group 3. Based on the FDA Snapshot algorithm, participants’ outcomes will be grouped into the following three categories:  HIV-1 RNA ≤1000 copies/mL  HIV-1 RNA >1000 copies/mL (also includes participants who discontinued study/TLD for Other Reasons [e.g., withdrew consent, loss to followup, moved, etc.] while >1000 copies/mL; and participants who changed ART)  No Virologic Data (participants will be grouped by the following reasons: on study but missing data in window; discontinued study/TLD due to AE or death; discontinued study/TLD for other reasons [e.g., withdrew consent, loss-tofollowup]) 2 Suppression of plasma HIV-1 RNA to ≤1000 copies/mL at months 12, 24, and 36. 3 Time to confirmed virologic failure (VF), defined as the time from start of TLD to the first HIV-1 RNA >1000 copies/mL at or after 6 months which is confirmed by the next HIV-1 RNA measurement also being >1000 copies/mL (irrespective of the time between the initial and confirmatory measurements provided that they are obtained on different days, and irrespective of ART being received at the times of these measurements). 4 Time to confirmed virologic failure (as defined above) with a new DTG resistance-associated mutation detected in population-based sequencing (i.e., one not present in the last population-based sequence obtained prior to initiating TLD). 5 Time from start of TLD to TLD discontinuation. 6 Time from start of TLD to TLD discontinuation due to toxicity. 7 Summary score of quality of life measure. 6-12 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kisumu Clinical Research Site Jaramogi Oginga Odinga Teaching and Referral Hospital Kemri Clinical Research Site PO BOX 1578 Kisumu Kisumu 40100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
PEPFAR US Department of State Washington United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor AIDS Clinical Trials Group Does not have a specific street address na United States of America Other Collaborative Groups
COLLABORATORS
Name Street address City Postal code Country
National Institute of Health 9000 Rockville Pike Bethesda Bethseda United States of America
Centers For Disease Control and Prevention 1600 Clifton Road Atlanta Atlanta United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Victor Mudhune vmudhune@kemricdc.org +254722687430 Kemri Clinical Research Center Jaramogi Oginga Odinga Teaching and Referral Hospital PO BOX 1578
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Pharmacist KEMRI CGHR
Role Name Email Phone Street address
Public Enquiries Evans Odipo eodipo@kemricdc.org +254733922213 Kemri Clinical Research Center Jaramogi Oginga Odinga Teachig and Referral Hospital PO BOX 1578
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Regulatory officer Kemri CGHR
Role Name Email Phone Street address
Scientific Enquiries Taraz Samandari tts0@cdc.gov +254703485481 Clinical Research Center Jaramogi Odinga Oginga Teaching and Referal Hospital PO BOX 1578
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya CDC Technical Advisor and Acting CRS Leader
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes This will be shared by the AIDS Clinical Trials Group as this is a multi-site trial Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol this is provided by the ACTG as its responsible for running and conduct of the trial At End of the study
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