Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of 2-Drug Therapy With Dolutegravir(DTG)/Rilpivirine(RPV) Fixed Dose Combination(FDC) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With NNRTI Mutation K103N
- Conditions
- HIV-1-infection
- Interventions
- Registration Number
- NCT05349838
- Lead Sponsor
- NEAT ID Foundation
- Brief Summary
HIV-1 infected subjects that experience virological failure while on non nucleoside reverse-transcriptase inhibitors (NNRTIs), including those with the K103N mutation, are usually switched to a boosted Protease Inhibitor (PI)-based regimen or other antiretroviral (ARV) combinations. The same is true for subjects who need to start antiretroviral therapy and have acquired virus that is already resistant to antiretrovirals. These "second line" combinations are often associated with numerous issues that can have a potential impact on the quality of life (QoL) of these patients. Therefore a simpler and better tolerated alternative second line treatment option would be a useful tool for the clinical management of these patients.
The aim of this study is to assess the efficacy and tolerability of a dual combined therapy of Dolutegravir (DTG) 50 mg Once Daily (OD) + Rilpivirine (RPV) 25 mg OD in virologically suppressed participants with previous virological failure with NNRTIs and having the clinically significant mutation K103N. The secondary objective of the study is to assess whether a simplification of the treatment in terms of pill burden, long term metabolic toxicity and potential for drug interactions improves the QOL of the participants. The study will also evaluate DTG \& RPV concentrations in the blood plus changes in cell associated virus.
In order to compare the first line treatment (boosted PI and/or other antiretroviral combinations) and the DTG+RPV combination, two thirds of study participants will be switched to DTG+RPV immediately and receive DTG+RPV for 96 weeks. The other third will be switched after 48 weeks of continuing on their first line treatment and receive DTG+RPV for 48 weeks. All participants will then be followed up for a further 30 days. Participants will be recruited from sites across Europe, and randomised onto either arm of the study. After randomisation, participants will attend approximately 10 visits over the course of two years.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 140
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description DTG/RPV FDC Regimen Dolutegravir & Rilpivirine 2 drug fixed dose combined therapy One combined Dolutegravir 50mg /Rilpivirine 25mg FDC tablet taken orally once daily Continued ART Regimen Dolutegravir & Rilpivirine 2 drug fixed dose combined therapy Patients will continue the current boosted PI regimen (or other antiretroviral combination) for 48 weeks. Patients will then be switched to one combined Dolutegravir/Rilpivirine FDC tablet taken orally once daily for 48 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With and Without Virological Suppression 48 weeks Virological Suppression is defined as \<50 copies/ml HIV RNA
- Secondary Outcome Measures
Name Time Method Changes in Renal Markers - Creatinine Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Renal markers evaluation - creatinine
Changes in Bone Markers - Alkaline Phosphatase Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Bone markers evaluation - Alkaline phosphatase
Number of Participants With and Without Virological Suppression week 96 Virological Suppression is defined as \<50 copies/ml HIV RNA
Changes in Blood Cell Counts - Red Blood Cells Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 red blood cell count evaluation
Changes in Blood Cell Counts - White Blood Cells Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 white blood cell count evaluation
Changes in Blood Cell Counts - Platelets Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 platelet count evaluation
Changes in Blood Cell Counts - Haemoglobin Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Haemoglobin count evaluation
Change From Baseline in Sodium Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Change from baseline in Sodium
Changes in Liver Levels - Bilirubin Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Liver level evaluation - bilirubin
Changes in Liver Levels - Alanine Aminotransferase (ALT) Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Liver level evaluation - ALT
Changes in Renal Markers - Creatinine Clearance (Estimated Glomerular Filtration Rate(eGFR)) Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Renal markers evaluation- creatinine clearance (eGFR)
Change From Baseline in Glucose Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Change from baseline in Glucose
Changes in Fasting Lipids From Baseline - Total Cholesterol Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Fasting lipids level evaluation - total cholesterol
Changes in Fasting Lipids From Baseline - High Density Lipoprotein (HDL) Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Fasting lipids level evaluation - HDL
Changes in Quality of Life Health Status Score Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Questionnaire (EQ-5D-3L) Mobility, Self-care, Usual activities, Pain/Discomfort and Anxiety/Depression are recorded on 3 point scale (tick boxes), which indicates the severity of problems the participant has with each of these activities. Patients will select No problems, Some problems or Extreme problems/Unable to perform. Patients also report their current Health State on a Scale from 1 to 100 on which the best state you can imagine is marked 100 and the worst state you can imagine is marked 0.
Changes in Patient Satisfaction - HIV Treatment Satisfaction Questionnaire (HIVTSQs) Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 HIV Treatment Satisfaction Questionnaire (HIVTSQs) Answers are recorded on a scale from 0 to 6, with 0 being least satisfied and 6 being most satisfied.
Number of Participants With Adverse Events - Baseline to Week 48 Baseline to week 48 Adverse Events reports (AEs, SAEs and treatment discontinuation)
Number of Drug Drug Interactions Baseline, week 24, week 48, week 96 Comparing the drug interaction outcomes between antiretroviral therapy and co-medications before and after the switch by using the www.hiv-druginteractions.org/ website (within the same study arm)
Changes in Fasting Lipids From Baseline - Triglycerides Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Fasting lipids level evaluation - triglycerides
Changes in Fasting Lipids From Baseline - Low Density Lipoprotein (LDL) Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Fasting lipids level evaluation - LDL
Changes in Vital Signs From Baseline - Systolic Blood Pressure Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Changes in Vital Signs from baseline - Systolic Blood Pressure
Changes in Vital Signs From Baseline - Diastolic Blood Pressure Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Changes in Vital Signs from baseline - Diastolic Blood Pressure
Changes in Vital Signs From Baseline - Pulse Rate Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Changes in Vital Signs from baseline - Pulse rate
Changes in Pittsburgh Sleep Quality Index (PSQI) Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 The PSQI measures several different aspects of sleep, with seven component scores and one composite score. The component scores include questions on subjective sleep quality, sleep latency (i.e., how long it takes to fall asleep), sleep duration, habitual sleep efficiency (i.e., the percentage of time in bed that one is asleep), sleep disturbances, use of sleeping medication, and daytime dysfunction.
Each component score of the PSQI ranges from 0 to 3, with 3 indicating the greatest dysfunction or disturbance to sleep. The seven component scores are then summed to obtain a global PSQI score, which ranges from 0 to 21. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficultiesNumber of Participants With Adverse Events - Week 48 to Week 96 From Week 48 to week 96 Adverse Events reports (AEs, SAEs and treatment discontinuation)
Change From Baseline in CD4 Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Change From Baseline in CD8 Cell Count Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Change from baseline to week 48, Change from week 48 to week 96; Change from baseline to week 96 in participants in the DTG/RPV FDC Regimen and Continued ART Regimen arms
Change From Baseline in Body Weight Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96 Change From Baseline in BMI Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96
Trial Locations
- Locations (29)
Institute of Tropical Medecine
🇧🇪Antwerp, Belgium
University Bonn
🇩🇪Bonn, Germany
Pitié-salpêtrière Hospital
🇫🇷Paris, France
CHU Hotel Dieu
🇫🇷Nantes, France
St Pierre University Hospital
🇧🇪Brussels, Belgium
Hospital Saint Louis
🇫🇷Paris, France
I.R.C.C.S San Raffaele Hospital
🇮🇹Milan, Italy
Hospital Universitari Vall d'Herbo
🇪🇸Barcelona, Spain
North Bristol NHS Trust, Southmead Hospital
🇬🇧Bristol, United Kingdom
Kings College Hospital London
🇬🇧London, United Kingdom
ASST GOM Niguarda Milano, Dep. Infectious Disease
🇮🇹Milano, Italy
ASST FBF SACCO- I Division of Infectious Diseases 1
🇮🇹Milan, Italy
Frankfurt University Hospital
🇩🇪Frankfurt, Germany
University Essen
🇩🇪Essen, Germany
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital General Universitario de Elche
🇪🇸Elche, Spain
Brighton & Sussex University NHS Trust
🇬🇧Brighton, United Kingdom
ASST FBF SACCO- I Division of Infectious Diseases 3
🇮🇹Milan, Italy
ICH Study Center, Hamburg
🇩🇪Hamburg, Germany
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
AAST delgi spedali civili di Brescia
🇮🇹Brescia, Italy
Infectious Diseases Unit Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario La Paz, Madrid
🇪🇸Madrid, Spain
Mortimer Market Centre
🇬🇧London, United Kingdom
Queen Elizabeth Hospital
🇬🇧London, United Kingdom
St Marys Hospital
🇬🇧London, United Kingdom
The Royal London Hospital
🇬🇧London, United Kingdom
Chelsea & Westminster Hospital
🇬🇧London, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom