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: www.pactr.org
Trial no.: PACTR201904781300573 Date of Approval: 10/04/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title VISEND
Official scientific title Virological Impact of Switching from Efavirenz and Nevirapine-based First-Line ART Regimens to Dolutegravir
Brief summary describing the background and objectives of the trial Background: In a public health setting, efforts must be made to provide universal access to the highest quality HIV treatment, taking into consideration the efficacy, tolerability, potency/durability, accessibility, and affordability of various treatment regimens. The WHO is committed to providing rapid updates when new scientific and programmatic information is available to better guide the optimal means of offering ART. Currently, there is no evidence on how to best manage the transition of individuals who are not virologically suppressed on NNRTI-based first line ART regimens to DTG-based ART. There is currently no study that has evaluated the clinical and virologic outcomes of these patients once they are transitioned from a failing dual NRTI plus single NNRTI combination to dual NRTI plus INSTI (DTG)-based regimen while maintaining the same two NRTIs. In addition, one cannot predict the outcomes based on available and published DTG switch studies as the study populations in these studies were individuals that were virologically suppressed. The DTG dual-therapy switch studies may only provide some inference on adequate virological outcomes to those patients who may be switched but only while failing one of their prescribed NRTIs. Those individuals who may be failing both prescribed NRTIs will essentially be receiving functional DTG monotherapy. However, even such inferences are just merely speculative as the protective effect of various NRTI backbones and type of NNRTI used are also not known. Only a study prospectively evaluating outcomes in such individuals being switched to INSTI (DTG)-based first line ART would provide such urgently needed definitive evidence. Primary Objective: Compare short- (24 and 48 weeks) and long-term (72, 96 and 144 weeks) virologic outcomes among HIV-positive, ART-treated adults switched from TDF/XTC/EFV or NVP-containing regimens to TDF or TAF/XTC/DTG-containing regimens with and without virologic suppression at time of switch.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) VISEND
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 15/04/2019
Actual trial start date 03/04/2019
Anticipated date of last follow up 30/04/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 1254
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL To be provided when the trial opens and results available (in keeping with WHO/other regulatory requirements RE: data sharing)
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 Randomised Simple randomization using a randomization table created by a computer software program 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
Control Group TLD Tenofovir 300 mgs OD / Lamuvidine 300 mgs OD / Dolutegravir 50 mgs OD Duration of the study and pending study results lifelong Arm A1 (baseline VL < 1000 copies/mL) 209 Active-Treatment of Control Group
Control Group TafED TAF 25 mgs OD. Emtricitabine (FTC) 150 mgs OD, plus DTG 50 mgs OD Duration of study; lifelong pending results of trial Arm A2 (Baseline VL < 1000 copies/mL) 209 Active-Treatment of Control Group
Experimental Group TLD Tenofovir 300 mgs OD, Lamuvidine (3TC) 300 mgs OD, plus DTG 50 mgs OD Duration of study; lifelong pending results of trial Arm B1a (Baseline VL > 1000 copies/mL) 209
Experimental Group TafED Tenofovir alafenamide (TAF) 25 mgs OD, Emtricitabine (FTC) 150 mgs OD, plus DTG 50 mgs OD Duration of study; lifelong pending results of trial Arm B1b (Baseline VL > 1000 copies/mL) 209
Control Group AZT 3TC plus LPV ritonavir AZT 300 mgs BID, 3TC 300 mgs OD, plus Lopinavir 400 Ritonavir & 100 mg tablets BID Duration of study; lifelong pending results of trial Arm B2a (Baseline VL > 1000 copies/mL) 209 Active-Treatment of Control Group
Control Group AZT 3TC plus Atazanavir and Ritonavir AZT 300 mgs BID, 3TC 300 mgs OD, plus Atazanavir 300 mgs OD and Ritonavir 100 mgs OD Duration of study; lifelong pending results of trial Arm B2b (BAseline VL > 1000 copies/mL) 209 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Participants will eligible for study participation if they meet the following criteria: 1. HIV-1 infection, as documented by confirmed licensed rapid test kit at any time prior to study entry 2. Taking TDF/XTC/EFV or NVP based ART 3. Male or female, age 18 or over 4. Ability and willingness to provide informed consent and willingness to comply with the requirements of the protocol, including being observed for 144 weeks on study, and complete all scheduled appointments and lab draws according to the national treatment guidelines and study protocol Participants will be excluded from participation if they meet any of the following criteria 1. HIV-2 infection 2. Signs or symptoms consistent with established cirrhosis 3. Pregnant or lactating or those who are actively trying to conceive, or who are not using a consistent and reliable method of birth control 4. Severe chronic diarrhoea lasting for more than 30 consecutive days at time of screening 5. Active Tuberculosis and on Rifampicin based anti-tuberculous therapy 6. History of any chronic or acute illness or other condition that in the opinion of the investigator would interfere with the conduct or completion of the study 7. Receiving a prohibited medication for treatment of another medical condition 8. Current enrolled in an experimental protocol, or is receiving an experimental medication or vaccine 9. Current alcohol abuse or illicit drug use that in the opinion of the investigator may interfere with the patient’s ability to comply with the protocol requirements 10. History or current diagnosis of a psychiatric illness or major depression 11. Exhibition non-adherence to prior medical care and treatments 12. ALT > 2.5 times the upper limit of normal at baseline 13. Creatinine clearance <50 ml/min at study enrolment 14. Compulsory detention (i.e. involuntary incarceration) at the time of screening and enrolment 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ 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 17/07/2018 University of Zambia Biomedical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Ridgeway Campus, Nationalist Road Lusaka 10101 Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. Virologic Endpoints • HIV-1 plasma RNA >1,000 copies/mL at week 144 2. Toxicity Endpoints • Grade 3 or 4 adverse event requiring discontinuation of therapy 144 weeks
Secondary Outcome 1. Virologic Endpoints • HIV-1 plasma RNA >1,000 copies/mL at weeks 24,48, 72, 96 and 144 • HIV-1 plasma RNA >50 copies/mL at weeks 24,48, 72, 96 and 144 • Presence of genotypic resistance mutations at the time of Virologic failure and/or week 48 in patients with a viral load > 1,000 copies/mL 2. Toxicity Endpoints • Grade 2 adverse event requiring medical intervention and/or therapy 24, 48, 72, 96, and 144 weeks
Secondary Outcome 3. To compare immunologic response (CD4 T cell increase) at 24 and 48 weeks among clients switched from TDF/XTC/EFV or NVP to TDF or TAF/XTC/ DTG with undetectable viral load to those with detectable viral load at the time of switch 4. To compare immunologic response (CD4 T cell increase) at 72,96 and 48 weeks among clients switched from TDF/XTC/EFV or NVP to TDF or TAF/XTC/ DTG with undetectable viral load to those with detectable viral load at the time of switch 5. To identify baseline genotypic drug resistance profiles among patients having plasma viral load values > 1,000 copies/mL switched from TDF/XTC/EFV or NVP to TDF or TAF/XTC/ DTG 6. To compare genotypic drug resistance patterns among patients having plasma viral load values > 1,000 copies/mL at 24, 48, 72, 96 and 144 weeks among patients with detectable viral loads (i.e. > 50 copies/mL) versus undetectable (i.e. < 50 copies/mL) at the time of regimen switch. 7. To assess the patient characteristics (clinical, laboratory, and socio-demographic) associated with detectable viremia at 24, 48, 72, 96 and 144 weeks among clients switched from TDF/XTC/EFV or NVP-containing regimens to TDF or TAF/XTC/ DTG-containing regimens. 8. To describe changes in longitudinal renal function (based on calculated creatinine clearance/estimated glomerular filtration rate (eGFR) using the CKD-EPI equation) at 24, 48, 72, 96 and 144 weeks among clients switched from TDF/XTC/EFV or NVP-containing regimens to TDF or TAF/XTC/ DTG-containing regimens. 9. To compare changes in eGFR at 12, 24 and 48 weeks among patients switched to TDF/XTC/ DTG-containing regimens as well as those switched to TAF/XTC/ DTG-containing regimens; specifically looking at potential differences in renal function parameters (i.e. urine albumin-to-creatinine ratio (uACR), eGFR, serum creatinine changes, etc.) among patients receiving TDF- versus TAF-based ART. 10. To compare virologic response (viral suppression rates) at 12,48,72, 96 and 144 weeks among clients switched from TDF/XTC/EFV or NVP to TDF or TAF/XTC/ DTG to those switched to AZT/3TC/LPV/r or ATV/r with viral load>1000 at the time of switch 12, 48, 72, 96, and 144 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University Teaching Hospital Nationalist Road Lusaka 10101 Zambia
Parirenyatwa Hospital Mazowe St Harare Zimbabwe
FUNDING SOURCES
Name of source Street address City Postal code Country
Mylan Laboratories Limited Plot No 564/A/22, Road No 92, Jubilee Hills, Hyderabad Telangana 500096 India
The Global Fund Ministry of Health, Ndeke House Lusaka 10101 Zambia
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor The Global Fund Ministry of Health, Ndeke House Lusaka 10101 Zambia Funding Agency
Primary Sponsor Mylan Laboratories Limited Plot No 564/A/22, Road No 92, Jubilee Hills, Hyderabad Telangani 500096 India Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Vanderbilt University Medical Center Vanderbilt University Medical Center, 1161 21st Avenue South, A2200, MCN Nashville 37232 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Lloyd B. Mulenga lbmulenga@yahoo.com +267977344604 University Teaching Hospital UTH, Nationalist Road
City Postal code Country Position/Affiliation
Lusaka 10101 Zambia Director and Consultant Physician Division of Infectious Diseases
Role Name Email Phone Street address
Scientific Enquiries C. William Wester william.wester@vumc.org +16158750145 Vanderbilt University Medical Center , Vanderbilt University Medical Center, 1161 21st Avenue South, A2200
City Postal code Country Position/Affiliation
Nashville 37232 United States of America Professor of Medicine Department of Medicine Division of Infectious Diseases
Role Name Email Phone Street address
Public Enquiries Lameck Chirwa lameckchirwa@yahoo.com +260977927497 University Teaching Hospital, Nationalist Road
City Postal code Country Position/Affiliation
Lusaka 10101 Zambia Trial Coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Yes, the VISEND study team plans to make IPD collected in this study, including data dictionaries, summary results, available to other researchers and we will do so at the end of the study. In addition, the VISEND team will also make the Study Protocol, Statistical Analysis Plan and Informed Consent forms available at the time of study completion. NOTE: At the time of manuscript submissions, the VISEND team will also provide links to all statistical analysis plans; at the time the manuscript is accepted for publication. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol End of study or at time of manuscript acceptance (please see above for details). We anticipate the study being completed April 30, 2023 but anticipate having numerous publications detailing study findings prior to the study closure date. All the data used in the study are available from public resources. The dataset (other pertinent study materials) can be made available on request from the corresponding author.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
URL to be provided once study ongoing, data analysis has commenced. 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
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 08/04/2019 Correction to include minimum age of 18 years Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s), 80 and over: 80+ Year Adolescent: 13 Year-18 Year, Adult: 19 Year-44 Year, Middle Aged: 45 Year(s)-64 Year(s), Aged: 65+ Year(s), 80 and over: 80+ Year
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Publication URL 08/04/2019 See Publication URL text To be provided when the trial opens and results available (in keeping with WHO/other regulatory requirements RE: data sharing)
Section Name Field Name Date Reason Old Value Updated Value
Reporting Plan to share IPD 08/04/2019 WHO requirement Undecided Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 08/04/2019 Requested during review and amended accordingly. Yes, the VISEND study team plans to make IPD collected in this study, including data dictionaries, summary results, available to other researchers and we will do so at the end of the study. In addition, the VISEND team will also make the Study Protocol, Statistical Analysis Plan and Informed Consent forms available at the time of study completion. NOTE: At the time of manuscript submissions, the VISEND team will also provide links to all statistical analysis plans; at the time the manuscript is accepted for publication.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 08/04/2019 WHO requirement End of study or at time of manuscript acceptance (please see above for details). We anticipate the study being completed April 30, 2023 but anticipate having numerous publications detailing study findings prior to the study closure date.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 08/04/2019 WHO requirement All the data used in the study are available from public resources. The dataset (other pertinent study materials) can be made available on request from the corresponding author.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD URL 08/04/2019 URL link to be provided once analysis ongoing/study has commenced. URL to be provided once study ongoing, data analysis has commenced.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 08/04/2019 WHO requirement Study Protocol, Statistical Analysis Plan, Informed Consent Form, Clinical Study Report, Analytic Code
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 02/08/2019 Study opened for enrollment on April 3rd, 2019 03 Apr 2019
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 02/08/2019 Opened for enrollment on April 3,2019 Active, not recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 19/10/2019 Change in power calculations, based on estimated effect size between arms. Updated by study biostatistician. 2346 1254
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 19/10/2019 Change in power calculations, based on estimated effect size between arms. Updated by study biostatistician. Control Group, TLD, Tenofovir 300 mgs OD / Lamuvidine 300 mgs OD / Dolutegravir 50 mgs OD, Duration of the study and pending study results lifelong , Arm A1 (baseline VL < 1000 copies/mL) , 482, Active-Treatment of Control Group Control Group, TLD, Tenofovir 300 mgs OD / Lamuvidine 300 mgs OD / Dolutegravir 50 mgs OD, Duration of the study and pending study results lifelong , Arm A1 (baseline VL < 1000 copies/mL) , 418, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 19/10/2019 Change in power calculations, based on estimated effect size between arms. Updated by study biostatistician. Control Group, TLD, Tenofovir 300 mgs OD / Lamuvidine 300 mgs OD / Dolutegravir 50 mgs OD, Duration of the study and pending study results lifelong , Arm A1 (baseline VL < 1000 copies/mL) , 418, Active-Treatment of Control Group Control Group, TLD, Tenofovir 300 mgs OD / Lamuvidine 300 mgs OD / Dolutegravir 50 mgs OD, Duration of the study and pending study results lifelong , Arm A1 (baseline VL < 1000 copies/mL) , 209, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 19/10/2019 Change in power calculations, based on estimated effect size between arms. Updated by study biostatistician. Control Group, TafED , TAF 25 mgs OD. Emtricitabine (FTC) 150 mgs OD, plus DTG 50 mgs OD , Duration of study; lifelong pending results of trial , Arm A2 (Baseline VL < 1000 copies/mL) , 482, Active-Treatment of Control Group Control Group, TafED , TAF 25 mgs OD. Emtricitabine (FTC) 150 mgs OD, plus DTG 50 mgs OD , Duration of study; lifelong pending results of trial , Arm A2 (Baseline VL < 1000 copies/mL) , 209, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 19/10/2019 Change in power calculations, based on estimated effect size between arms. Updated by study biostatistician. Experimental Group, TLD, Tenofovir 300 mgs OD, Lamuvidine (3TC) 300 mgs OD, plus DTG 50 mgs OD , Duration of study; lifelong pending results of trial , Arm B1a (Baseline VL > 1000 copies/mL), 482, Experimental Group, TLD, Tenofovir 300 mgs OD, Lamuvidine (3TC) 300 mgs OD, plus DTG 50 mgs OD , Duration of study; lifelong pending results of trial , Arm B1a (Baseline VL > 1000 copies/mL), 209,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 19/10/2019 Change in power calculations, based on estimated effect size between arms. Updated by study biostatistician. Experimental Group, TafED, Tenofovir alafenamide (TAF) 25 mgs OD, Emtricitabine (FTC) 150 mgs OD, plus DTG 50 mgs OD , Duration of study; lifelong pending results of trial , Arm B1b (Baseline VL > 1000 copies/mL) , 482, Experimental Group, TafED, Tenofovir alafenamide (TAF) 25 mgs OD, Emtricitabine (FTC) 150 mgs OD, plus DTG 50 mgs OD , Duration of study; lifelong pending results of trial , Arm B1b (Baseline VL > 1000 copies/mL) , 209,