Evaluation of Low-dose Darunavir in a Switch Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Darunavir
* Drug: Lopinavir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| Time to virologic failure |  | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antiretroviral Agents, Treatment, Viral Load