Human Immunodeficiency VirusPhase 3NCT01792570
DRV/r + RPV QD: Efficacy and Toxicity Reduction
A Phase 3 study testing RPV + DRV/r and continue the PI/r-containing HAART. in people with Human Immunodeficiency Virus, run by ASST Fatebenefratelli Sacco at 12 sites in Italy.
Trial summary
Clinical approach to HIV infection treatment is based on the use of highly active antiretroviral therapies (HAART) and recent national and international guidelines for guiding HIV therapy recommend the use of triple-combination therapy using antiretrovirals with 2 nucleos(t)ide inhibitors [N(n)RTI] as backbone plus a… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Human Immunodeficiency Virus
- What is being tested?
- RPV + DRV/r and continue the PI/r-containing HAART.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 12 sitesItaly
- Study dates
- 30 Sep 2014to 31 Dec 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult HIV+ subjects (>18 years old), giving and signing an informed consent;
- Any HAART treatment for at least 12 months;
- Current treatment with a PI/r-containing regimen initiated at least 6 months earlier;
- HIV-RNA <50 cp/mL for at least 3 months, without viral blip due to virologic failure at any time;
- Any nadir CD4 lymphocytes;
- Current CD4 count > 100 cell/uL;
- eGFRs >60 mL/min/1.73 m2.
Who cannot join
- Previous drug resistance genotypic test showing the presence of any RPV (RT: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, M230I/L) or DRV (protease: V11I, V32I, L33F, I47V, I50V, I54M/L, T74P, L76V, I84V, L89V) resistance associated mutation (RAM), according to the November 2011 IAS-USA list;
- Child-Pugh C or grade 3-4 AST or ALT values;
- Acute cardiovascular event within 6 months;
- AIDS event within 6 months;
- Current IVDU;
- HBsAg +;
- Pregnancy or lactation.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Italy12 sites
Clinica delle Malattie Infettive, Policlinico Universitario
Bari, BA
Divisione di Malattie Infettive, Ospedale S. Maria Annunziata, Antella
Florence, FI
Clinica delle Malattie Infettive, Ospedale San Martino, Università degli Studi
Genova, GE
Divisione Clinicizzata di Malattie Infettive dell'Università degli Studi, Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco"
Milan, MI, 20157
I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"
Milan, MI, 20157
Clinica Malattie Infettive, Policlinico Universitario
Modena, MO
Divisione di Malattie Infettive, Ospedale San Gerardo
Monza, MB
U.O. Malattie Infettive, Policlinico S. Matteo
Pavia, PV
Clinica delle Malattie Infettive, Policlinico "Tor Vergata"
Roma, RM
Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore
Roma, RM
U.O. Malattie Infettive, Azienda Policlinico Umberto I, Università degli Studi "La Sapienza"
Roma, RM
Clinica delle Malattie Infettive, Ospedale Amedeo di Savoia, Università degli Studi
Torino, TO
About this study
Official title: Strategic Study of Dual-therapy With Darunavir/Ritonavir and Rilpivirine QD Versus Triple-therapy in Patients With Suppressed Viral Load: Virological Efficacy and Evaluation of Non-HIV Related Morbidity.
Clinical approach to HIV infection treatment is based on the use of highly active antiretroviral therapies (HAART) and recent national and international guidelines for guiding HIV therapy recommend the use of triple-combination therapy using antiretrovirals with 2 nucleos(t)ide inhibitors [N(n)RTI] as backbone plus a third drug to be chosen among a boosted protease inhibitor (PI/r), a nonnucleoside inhibitor (NNRTI) or an integrase inhibitor (II).
In spite of evident efficacy of HAART, as demonstrated by survival increasing, long term side effects, as for example the impact on renal function, remain principal problem.
Read more
In patient with risk factor for renal disease, a reduction of eGRF (estimated Glomerular Filtration Rate) between 90 and 60 mL/min/1,73 m2 could be already considered as a risk condition [1,2].
Efficacy of HAART, with increase of media survival and the parallel decrease of mortality, has underlined the necessity to reflect on long term HAART effects [3].
There are many evidences of HAART-related toxicity that, in spite of the necessity of a life-saving therapy, focus on the additional costs of this situation, in terms of health as well as in terms of economic costs.
Particular attention has been focused on the impact of some drugs on renal function, as tenofovir, especially on tubule, without forgetting the modification of lipid and bone metabolisms.
According to further studies which have evidenced the potential of some recently introduced molecules [4,5], the investigators had the need to realize a study to deepen the feasibility of a dual-therapy that permit to exclude NRTIs from the backbone, with the aim to prevent NRTIs-related long-term toxicity.
The investigators have designed a prospective randomized controlled trial, open-label, with a duration of 96 weeks, to compare the efficacy of a dual-therapy based on rilpivirine 25mg plus darunavir 800mg/ritonavir 100mg QD, in HIV-positive subjects with suppressed viremia from at least 3 months. In fact, there are a few data about association of these drugs, which it has been shown to be safe, well tolerated, and with a strong pharmacological synergy, without nucleos(t)idic backbone, while the necessity to minimize the costs toxicity-related is becoming increasingly compelling.
According to clinical experience and literature data, the investigators hope this study shows positive results in term of immune-virological efficacy, as well as in term of decrease of VACS index - a complex parameter which has the purpose to quantify general organic decay - and markers of lipid and bone metabolism, in group which receives dual-therapy versus the group with standard therapy.
Read the detailed description
Pilot, phase III prospective, randomized, open-label, multicentric controlled study, which will offer a novel dual-therapy regimen including RPV 25mg + DRV 800mg/rtv 100mg QD to HIV+ subjects with suppressed viremia.
132 HIV+ subjects will be randomized, 1:1, to switch to RPV+DRV/r versus continue triple-drug therapy. Subjects will be switched from any PI/r-containing regimen.
The duration of the study is 96 weeks and patients will be stratified according to their HCV serostatus (Ab positive or negative), age (> or < 50 years), and immunological status (CD4<200/µL; CD4=200-500/µL; CD4>500/µL). It is planned to enroll at least 30% of female subjects.
Follow-up visits will be performed at 4, 8, 12, 24, 36, 48, 60, 72, and 96 weeks (laboratory and physical examination).
Effectiveness will be measured by determination of HIV-RNA, safety will be evaluated by determination of AST, ALT, creatinine, plasmatic and urinary phosphate, albuminuria, total cholesterol, HDL and LDL cholesterol, triglycerides at the follow-up visits.
- Conditions
- Human Immunodeficiency Virus
- Being tested
- RPV + DRV/r, continue the PI/r-containing HAART.
- Keywords
- HIV-1, darunavir, rilpivirine, strategic study
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RPV + DRV/rDrug
Also called RVP: rilpivirine; brand name: EdurantTM., DRV: darunavir; brand name: PrezistaTM.
Switch to dual HAART
continue the PI/r-containing HAART.Drug
Also called the drugs will depend on the successful regimen.
Continue the on-going triple drug HAART.
| Study group | Role | What they receive |
|---|---|---|
| RPV + DRV/r | Experimental | switch to RPV + DRV/r Receives: Drug: RPV + DRV/r |
| continue the PI/r-containing HAART. | Active comparator | continue the PI/r-containing HAART Receives: Drug: continue the PI/r-containing HAART. |
What is being measured
The primary outcome is the main question the study is designed to answer.
HIV-RNA < 50 cp/mL
Responders: HIV+ subjects with HIV-RNA < 50 cp/mL at week 48 according to the intention-to-treat (ITT-TLOVR) approach.
Measured: Week 48
Secondary outcomes (1)
ACTG grade III and IV events.
Safety will be assessed through the number of ACTG grade III and IV in the specified safety parameters.
Measured: over 96 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2013 (estimated)
- Study start30 Sep 2014
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- ASST Fatebenefratelli Sacco
- Sponsor type
- University, hospital or other
- Collaborators
- Elisa Colella, M.D., Valentina Di Cristo, M.D., Massimo Galli, M.D.
- Responsible party
- Principal investigator, Stefano Rusconi, ASST Fatebenefratelli Sacco
- Investigators
- Stefano Rusconi, M.D., Principal investigator, DIBIC "Luigi Sacco", Università degli Studi di Milano, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01792570
- Sponsor's protocol ID
- HLS03/2012
- Status last verified
- Mar 2020
- First submitted
- 7 Feb 2013
- Last updated
- 2 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Maggi P, Bartolozzi D, Bonfanti P, Calza L, Cherubini C, Di Biagio A, Marcotullio S, Montella F, Montinaro V, Mussini C, Narciso P, Rusconi S, Vescini F. Renal complications in HIV disease: between present and future. AIDS Rev. 2012 Jan-Mar;14(1):37-53.
PubMed 22297503Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K. Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med. 2012 Jun 5;156(11):785-95. doi: 10.7326/0003-4819-156-11-201203200-00391. Epub 2012 Feb 6.
PubMed 22312131Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res. 2010 Jan;85(1):1-18. doi: 10.1016/j.antiviral.2009.10.002. Epub 2009 Dec 16.
PubMed 20018391Burgos J, Crespo M, Falco V, Curran A, Imaz A, Domingo P, Podzamczer D, Mateo MG, Van den Eynde E, Villar S, Ribera E. Dual therapy based on a ritonavir-boosted protease inhibitor as a novel salvage strategy for HIV-1-infected patients on a failing antiretroviral regimen. J Antimicrob Chemother. 2012 Jun;67(6):1453-8. doi: 10.1093/jac/dks057. Epub 2012 Feb 29.
PubMed 22378681Clumeck N, Cahn P, Molina JM, Mills A, Nijs S, Vingerhoets J, Witek J. Virological response with fully active etravirine: pooled results from the DUET-1 and DUET-2 trials. Int J STD AIDS. 2010 Nov;21(11):738-40. doi: 10.1258/ijsa.2010.010139.
PubMed 21187353
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Strategic Study of Dual-therapy With Darunavir/Ritonavir and Rilpivirine QD Versus Triple-therapy in Patients With Suppressed Viral Load: Virological Efficacy and Evaluation of Non-HIV Related Morbidity.
- ClinicalTrials.gov ID
- NCT01792570
- Acronym / sponsor ID
- HLS03/2012
- Conditions
- Human Immunodeficiency Virus
- Keywords
- HIV-1, darunavir, rilpivirine, strategic study
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- ASST Fatebenefratelli SaccoUniversity, hospital or other
- Collaborators
- Elisa Colella, M.D., Valentina Di Cristo, M.D., Massimo Galli, M.D.
- Study start
- 30 Sep 2014 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 15 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clinical approach to HIV infection treatment is based on the use of highly active antiretroviral therapies (HAART) and recent national and international guidelines for guiding HIV therapy recommend the use of triple-combination therapy using antiretrovirals with 2 nucleos(t)ide inhibitors [N(n)RTI] as backbone plus a third drug to be chosen among a boosted protease inhibitor (PI/r), a nonnucleoside inhibitor (NNRTI) or an integrase inhibitor (II).
In spite of evident efficacy of HAART, as demonstrated by survival increasing, long term side effects, as for example the impact on renal function, remain principal problem.
In patient with risk factor for renal disease, a reduction of eGRF (estimated Glomerular Filtration Rate) between 90 and 60 mL/min/1,73 m2 could be already considered as a risk condition [1,2].
Efficacy of HAART, with increase of media survival and the parallel decrease of mortality, has underlined the necessity to reflect on long term HAART effects [3].
There are many evidences of HAART-related toxicity that, in spite of the necessity of a life-saving therapy, focus on the additional costs of this situation, in terms of health as well as in terms of economic costs.
Particular attention has been focused on the impact of some drugs on renal function, as tenofovir, especially on tubule, without forgetting the modification of lipid and bone metabolisms.
According to further studies which have evidenced the potential of some recently introduced molecules [4,5], the investigators had the need to realize a study to deepen the feasibility of a dual-therapy that permit to exclude NRTIs from the backbone, with the aim to prevent NRTIs-related long-term toxicity.
The investigators have designed a prospective randomized controlled trial, open-label, with a duration of 96 weeks, to compare the efficacy of a dual-therapy based on rilpivirine 25mg plus darunavir 800mg/ritonavir 100mg QD, in HIV-positive subjects with suppressed viremia from at least 3 months. In fact, there are a few data about association of these drugs, which it has been shown to be safe, well tolerated, and with a strong pharmacological synergy, without nucleos(t)idic backbone, while the necessity to minimize the costs toxicity-related is becoming increasingly compelling.
According to clinical experience and literature data, the investigators hope this study shows positive results in term of immune-virological efficacy, as well as in term of decrease of VACS index - a complex parameter which has the purpose to quantify general organic decay - and markers of lipid and bone metabolism, in group which receives dual-therapy versus the group with standard therapy.
Detailed description
Pilot, phase III prospective, randomized, open-label, multicentric controlled study, which will offer a novel dual-therapy regimen including RPV 25mg + DRV 800mg/rtv 100mg QD to HIV+ subjects with suppressed viremia.
132 HIV+ subjects will be randomized, 1:1, to switch to RPV+DRV/r versus continue triple-drug therapy. Subjects will be switched from any PI/r-containing regimen.
The duration of the study is 96 weeks and patients will be stratified according to their HCV serostatus (Ab positive or negative), age (> or < 50 years), and immunological status (CD4<200/µL; CD4=200-500/µL; CD4>500/µL). It is planned to enroll at least 30% of female subjects.
Follow-up visits will be performed at 4, 8, 12, 24, 36, 48, 60, 72, and 96 weeks (laboratory and physical examination).
Effectiveness will be measured by determination of HIV-RNA, safety will be evaluated by determination of AST, ALT, creatinine, plasmatic and urinary phosphate, albuminuria, total cholesterol, HDL and LDL cholesterol, triglycerides at the follow-up visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RPV + DRV/r | Experimental | Drug: RPV + DRV/rswitch to RPV + DRV/r |
| continue the PI/r-containing HAART. | Active comparator | Drug: continue the PI/r-containing HAART.continue the PI/r-containing HAART |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult HIV+ subjects (>18 years old), giving and signing an informed consent;
- Any HAART treatment for at least 12 months;
- Current treatment with a PI/r-containing regimen initiated at least 6 months earlier;
- HIV-RNA <50 cp/mL for at least 3 months, without viral blip due to virologic failure at any time;
- Any nadir CD4 lymphocytes;
Key exclusion criteria (7 listed)
- Previous drug resistance genotypic test showing the presence of any RPV (RT: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, M230I/L) or DRV (protease: V11I, V32I, L33F, I47V, I50V, I54M/L, T74P, L76V, I84V, L89V) resistance associated mutation (RAM), according to the November 2011 IAS-USA list;
- Child-Pugh C or grade 3-4 AST or ALT values;
- Acute cardiovascular event within 6 months;
- AIDS event within 6 months;
- Current IVDU;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RPV + DRV/rAlso: RVP: rilpivirine; brand name: EdurantTM., DRV: darunavir; brand name: PrezistaTM.Switch to dual HAART | Drug | RPV + DRV/r |
| continue the PI/r-containing HAART.Also: the drugs will depend on the successful regimen.Continue the on-going triple drug HAART. | Drug | continue the PI/r-containing HAART. |
Primary outcome
HIV-RNA < 50 cp/mL
Time frame: Week 48
Responders: HIV+ subjects with HIV-RNA < 50 cp/mL at week 48 according to the intention-to-treat (ITT-TLOVR) approach.
1 secondary outcome
ACTG grade III and IV events.
Time frame: over 96 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2020.
- Background: PubMed 22297503Maggi P, Bartolozzi D, Bonfanti P, Calza L, Cherubini C, Di Biagio A, Marcotullio S, Montella F, Montinaro V, Mussini C, Narciso P, Rusconi S, Vescini F. Renal complications in HIV disease: between present and future. AIDS Rev. 2012 Jan-Mar;14(1):37-53.
- Background: PubMed 22312131Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K. Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med. 2012 Jun 5;156(11):785-95. doi: 10.7326/0003-4819-156-11-201203200-00391. Epub 2012 Feb 6.
- Background: PubMed 20018391Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res. 2010 Jan;85(1):1-18. doi: 10.1016/j.antiviral.2009.10.002. Epub 2009 Dec 16.
- Background: PubMed 22378681Burgos J, Crespo M, Falco V, Curran A, Imaz A, Domingo P, Podzamczer D, Mateo MG, Van den Eynde E, Villar S, Ribera E. Dual therapy based on a ritonavir-boosted protease inhibitor as a novel salvage strategy for HIV-1-infected patients on a failing antiretroviral regimen. J Antimicrob Chemother. 2012 Jun;67(6):1453-8. doi: 10.1093/jac/dks057. Epub 2012 Feb 29.
- Background: PubMed 21187353Clumeck N, Cahn P, Molina JM, Mills A, Nijs S, Vingerhoets J, Witek J. Virological response with fully active etravirine: pooled results from the DUET-1 and DUET-2 trials. Int J STD AIDS. 2010 Nov;21(11):738-40. doi: 10.1258/ijsa.2010.010139.
- Individual participant dataSharing planned: Yes
Related trials for Human Immunodeficiency Virus
Recruiting
The Trans-Led Care Study
Substance Abuse, Substance Addiction
RecruitingObservational study
Clinical and Immunologic Monitoring of Patients With Known or Suspected HIV Infection
HIV
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 1
AMC 120, Glofitamab Plus Chemoimmunotherapy in Newly Diagnosed HIV-Associated Large B-Cell Lymphoma (The "Glofit-RCHOP Study")
AIDS-Related Diffuse Large B-cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefano Rusconi, M.D. principal investigator
DIBIC "Luigi Sacco", Università degli Studi di Milano, Italy
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RPV + DRV/r and continue the PI/r-containing HAART. in people with Human Immunodeficiency Virus, run by ASST Fatebenefratelli Sacco at 12 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HIV-RNA < 50 cp/mL (time frame: Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01792570, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2020.