Evaluation of Low-dose Darunavir in a Switch Study (DRV)

A Randomised, Open Label Switch Study Comparing Darunavir/Ritonavir 400mg/100mg Daily With Lopinavir/Ritonavir 800mg/200mg Daily, in HIV-positive Participants

This is a switch study to assess the non-inferiority (in terms of efficacy and safety) of darunavir (boosted with ritonavir, DRV/r 400mg/100mg daily) when compared with lopinavir (boosted with ritonavir, LPV/r total dose 800mg/200mg daily), in combination with a nucleoside backbone, administered as a second line therapy in HIV positive individuals.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Darunavir; Drug: Lopinavir

Detailed Description

This is an open label randomised, parallel group, phase 3b, switch study to demonstrate non-inferiority of low-dose boosted darunavir (DRV/RTV 400/100 mg once daily) compared with boosted lopinavir-based (LPV/RTV 800/200 mg daily) second-line regimens when administered over 48 weeks in combination with two nucleos(t)ide reverse transcriptase inhibitors in patients infected with HIV-1 who are virologically suppressed and stable on a standard second-line regimen. All medications will be provided in an open-label design. Patients who are virologically suppressed and stable on a standard second-line regimen will be recruited for the study. There are concerns that switching these patients may result in virological failure as the study aimed at demonstrating non-inferiority of darunavir compared with Lopinavir. In such cases, the investigator will ensure that virological failures are investigated and patients are switched back to standard of care immediately. Participants will be patients who are receiving HIV treatment in public clinics. Interested patients will be invited to the study, information given, and only those who will give written informed consent will be screened, and if eligible enrolled into the study. Each enrolled participant will be follow-up at week 4, 12, 24, 36, and 48 (exit visit) from enrolment date. Data will be collected using ethics-approved worksheets, and captured into REDCap. The data manager will ensure data are correct and complete by performing data verifications - physical and electronic. Internal quality control will be performed by dedicated staff based on the study quality plan to be implemented. The external study monitor will perform 100% eligibility checks on all signed informed consents in addition to other source verifications during her periodic site visits according to the monitoring plan to be implemented. Findings from the monitor will be implemented in the form of data/procedure corrections per good clinical practice, and all relevant staff trained and documented accordingly. Participants' records will be coded and stored in a lockable cabinet. Only study staff will have access to participants' records. All electronic documents relating to the study will be stored in password-protected computers and only accessible to study staff. Study staff are not allowed to share password among themselves or with anyone outside the study team. Designed in non-inferiority fashion, this study will enrol approximately 300 participants for 80% power to detect a 10% non-inferiority margin in the per protocol (PP) analysis. A Data Safety Management Board (DSMB) will oversee and review the interim data report. At the close of the study, results will be disseminated to participants, and the scientific community, as well as updated on clinicaltrial.gov.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • Charlotte Maxeke Johannesburg Academic Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant is aged ≥18 years
• Participant weight >40kg
• Participant is on a LPV/r-containing regimen for at least 6 months with no history of other protease inhibitors
• Participant has a plasma HIV-1 RNA level <50 copies/mL in the last 60 days
• Participant is informed and has the ability to comprehend the full nature and purpose of the study, and give voluntary written informed consent before inclusion in the study

Exclusion Criteria:

• Participants who are taking any antiretrovirals other than nucleoside/nucleotide reverse transcriptase inhibitors and LPV/r
• Any prior history of genotype-documented protease inhibitor resistance
• Participants who are taking rifampicin or any other therapy with major cytochrome P450 interactions, within the last month
• Participants who are allergic to sulphonamides
• Participants who have a current history of drug or alcohol abuse that, in the opinion of the investigator, may be an impediment to participant adherence to the protocol
• Female participants who are currently pregnant or breastfeeding
• Female participants desiring pregnancy during the next year
• Participants who have a strong likelihood of relocating far enough to make access to the study site difficult
• Any condition(s) or laboratory report that, in the opinion of the investigator, might put the participant at risk, or interfere with the study objectives or the participant's adherence to study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Darunavir; Darunavir/Ritonavir 400/100mg once daily	Drug: Darunavir; Darunavir/ritonavir 400/100mg (DRV/r) once daily plus nucleoside/nucleotide reverse transcriptase inhibitors.; Other Names: Boosted darunavir (DRV/r)
Active Comparator: Lopinavir; Lopinavir/Ritonavir 400/100mg twice daily	Drug: Lopinavir; Lopinavir/ritonavir 400/100mg (LPV/r) twice daily plus nucleoside/nucleotide reverse transcriptase inhibitors.; Other Names: Boosted lopinavir (LVP/r)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with undetectable HIV-1 RNA levels	Week 48
Number of participants with certain adverse events related to the treatment	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to virologic failure	Week 48

Other Outcome Measures

Outcome Measure	Time Frame
Lipids measure	Baseline, Week 24 and 48
Fasting glucose measure	Baseline and Week 48
Creatinine clearance measure	Baseline, Week 12, 24, and 48

Collaborators and Investigators

• Sponsor: Willem Daniel Francois Venter
• Collaborators: Medical Research Council, South Africa

Publications and helpful links

General Publications

• Draaijer M, Lalla-Edward ST, Venter WDF, Vos A. Phone Calls to Retain Research Participants and Determinants of Reachability in an African Setting: Observational Study. JMIR Form Res. 2020 Sep 30;4(9):e19138. doi: 10.2196/19138.
• Venter WDF, Moorhouse M, Sokhela S, Serenata C, Akpomiemie G, Qavi A, Mashabane N, Arulappan N, Sim JW, Sinxadi PZ, Wiesner L, Maharaj E, Wallis C, Boyles T, Ripin D, Stacey S, Chitauri G, Hill A. Low-dose ritonavir-boosted darunavir once daily versus ritonavir-boosted lopinavir for participants with less than 50 HIV RNA copies per mL (WRHI 052): a randomised, open-label, phase 3, non-inferiority trial. Lancet HIV. 2019 Jul;6(7):e428-e437. doi: 10.1016/S2352-3018(19)30081-5. Epub 2019 Jun 12.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2016
• Primary Completion (Actual): May 16, 2018
• Study Completion (Actual): May 16, 2018

Study Registration Dates

• First Submitted: January 28, 2016
• First Submitted That Met QC Criteria: February 1, 2016
• First Posted (Estimate): February 2, 2016

Study Record Updates

• Last Update Posted (Actual): June 26, 2018
• Last Update Submitted That Met QC Criteria: June 21, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Treatment; Viral Load; Antiretroviral Agents
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Lopinavir; Darunavir
• Other Study ID Numbers: WRHI052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided