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DRV/r + RPV QD: Efficacy and Toxicity Reduction

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ClinicalTrials.gov Identifier: NCT01792570
Recruitment Status : Completed
First Posted : February 15, 2013
Last Update Posted : April 2, 2020
Sponsor:
Collaborators:
Elisa Colella, M.D.
Valentina Di Cristo, M.D.
Massimo Galli, M.D.
Information provided by (Responsible Party):
Stefano Rusconi, ASST Fatebenefratelli Sacco

Brief 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 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.


Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: RPV + DRV/r Drug: continue the PI/r-containing HAART. Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : September 30, 2014
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: RPV + DRV/r
switch to RPV + DRV/r
Drug: RPV + DRV/r
Switch to dual HAART
Other Names:
  • RVP: rilpivirine; brand name: EdurantTM.
  • DRV: darunavir; brand name: PrezistaTM.

Active Comparator: continue the PI/r-containing HAART.
continue the PI/r-containing HAART
Drug: continue the PI/r-containing HAART.
Continue the on-going triple drug HAART.
Other Name: the drugs will depend on the successful regimen.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. ACTG grade III and IV events. [ Time Frame: over 96 weeks. ]
    Safety will be assessed through the number of ACTG grade III and IV in the specified safety parameters.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01792570


Locations
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Italy
Clinica delle Malattie Infettive, Policlinico Universitario
Bari, BA, Italy
Divisione di Malattie Infettive, Ospedale S. Maria Annunziata, Antella
Firenze, FI, Italy
Clinica delle Malattie Infettive, Ospedale San Martino, Università degli Studi
Genova, GE, Italy
Divisione di Malattie Infettive, Ospedale San Gerardo
Monza, MB, Italy
Divisione Clinicizzata di Malattie Infettive dell'Università degli Studi, Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco"
Milano, MI, Italy, 20157
I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"
Milano, MI, Italy, 20157
Clinica Malattie Infettive, Policlinico Universitario
Modena, MO, Italy
U.O. Malattie Infettive, Policlinico S. Matteo
Pavia, PV, Italy
Clinica delle Malattie Infettive, Policlinico "Tor Vergata"
Roma, RM, Italy
Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore
Roma, RM, Italy
U.O. Malattie Infettive, Azienda Policlinico Umberto I, Università degli Studi "La Sapienza"
Roma, RM, Italy
Clinica delle Malattie Infettive, Ospedale Amedeo di Savoia, Università degli Studi
Torino, TO, Italy
Sponsors and Collaborators
ASST Fatebenefratelli Sacco
Elisa Colella, M.D.
Valentina Di Cristo, M.D.
Massimo Galli, M.D.
Investigators
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Principal Investigator: Stefano Rusconi, M.D. DIBIC "Luigi Sacco", Università degli Studi di Milano, Italy
Publications:
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Responsible Party: Stefano Rusconi, Associate professor in infectious diseases, ASST Fatebenefratelli Sacco
ClinicalTrials.gov Identifier: NCT01792570    
Other Study ID Numbers: HLS03/2012
First Posted: February 15, 2013    Key Record Dates
Last Update Posted: April 2, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Keywords provided by Stefano Rusconi, ASST Fatebenefratelli Sacco:
HIV-1
darunavir
rilpivirine
strategic study
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Darunavir
Rilpivirine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors