DRV/r + RPV QD: Efficacy and Toxicity Reduction

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2013 by Ospedale L. Sacco – Polo Universitario
Sponsor:
Collaborators:
Elisa Colella, M.D.
Valentina Di Cristo, M.D.
Massimo Galli, M.D.
Information provided by (Responsible Party):
Stefano Rusconi, Ospedale L. Sacco - Polo Universitario
ClinicalTrials.gov Identifier:
NCT01792570
First received: February 7, 2013
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

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.

These results could stimulate further studies on less aggressive and however effective therapeutic regimens, with more sustainable biological and economic costs.


Condition Intervention Phase
HIV-positive Subjects With HIV-RNA <50 Copies/mL
Drug: RPV + DRV/r
Drug: subjects will continue the PI/r-containing regimen that is on-going at the time of enrollment.
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Ospedale L. Sacco – Polo Universitario:

Primary Outcome Measures:
  • HIV-RNA < 50 cp/mL [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Responders: HIV+ subjects with HIV-RNA < 50 cp/mL at week 48 according to the intention-to-treat (ITT-TLOVR) approach.


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


Estimated Enrollment: 132
Study Start Date: March 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RPV + DRV/r
switch to RPV + DRV/r
Drug: RPV + DRV/r
Other Names:
  • RVP: rilpivirine; brand name: EdurantTM.
  • DRV: darunavir; brand name: PrezistaTM.
Active Comparator: PI/ritonavir-containing antiretroviral triple drug therapy
the control arm will continue the protease inhibitor (PI)/r-containing triple drug therapy that is currently on-going.
Drug: subjects will continue the PI/r-containing regimen that is on-going at the time of enrollment.
Other Name: the drugs will depend on the successful regimen that is already administerd to the enrolled subject.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01792570

Contacts
Contact: Stefano - Rusconi, M.D. 0039 02 39042949 stefano.rusconi@unimi.it

Locations
Italy
Clinica delle Malattie Infettive, Policlinico Universitario Not yet recruiting
Bari, BA, Italy
Contact: Gioacchino Angarano, M.D.       g.angarano@clininf.uniba.it   
Principal Investigator: Gioacchino Angarano, M.D.         
Divisione di Malattie Infettive, Ospedale S. Maria Annunziata, Antella Not yet recruiting
Firenze, FI, Italy
Contact: Sergio Lo Caputo, M.D.       sergio.locaputo@asf.toscana.it   
Principal Investigator: Sergio Lo Caputo, M.D.         
Clinica delle Malattie Infettive, Ospedale San Martino, Università degli Studi Not yet recruiting
Genova, GE, Italy
Contact: Antonio Di Biagio, M.D.       antonio.dibiagio@hsanmartino.it   
Principal Investigator: Antonio Di Biagio, M.D.         
Divisione di Malattie Infettive, Ospedale San Gerardo Not yet recruiting
Monza, MB, Italy
Contact: Andrea Gori, M.D.       andrea.gori@unimib.it   
Principal Investigator: Andrea Gori, M.D.         
I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco" Not yet recruiting
Milano, MI, Italy, 20157
Contact: Giuliano Rizzardini, M.D.       rizzardini.giuliano@hsacco.it   
Principal Investigator: Giuliano Rizzardini, M.D.         
Divisione Clinicizzata di Malattie Infettive dell'Università degli Studi, Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco" Not yet recruiting
Milano, MI, Italy, 20157
Contact: Stefano Rusconi, M.D.       stefano.rusconi@unimi.it   
Contact: Elisa Colella, M.D.       elisa_colella@yahoo.it   
Principal Investigator: Stefano Rusconi, M.D.         
Clinica Malattie Infettive, Policlinico Universitario Not yet recruiting
Modena, MO, Italy
Contact: Cristina Mussini, M.D.       crimuss@unimore.it   
Principal Investigator: Cristina Mussini, M.D.         
U.O. Malattie Infettive, Policlinico S. Matteo Not yet recruiting
Pavia, PV, Italy
Contact: Renato Maserati, M.D.       rmaserati@smatteo.pv.it   
Principal Investigator: Renato Maserati, M.D.         
U.O. Malattie Infettive, Azienda Policlinico Umberto I, Università degli Studi "La Sapienza" Not yet recruiting
Roma, RM, Italy
Contact: Vincenzo Vullo, M.D.       vincenzo.vullo@uniroma1.it   
Contact: Gabriella D'Ettorre, M.D.       gabriella.dettorre@uniroma1.it   
Principal Investigator: Vincenzo Vullo, M.D.         
Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore Not yet recruiting
Roma, RM, Italy
Contact: Simona Di Giambenedetto, M.D.       simona.digiambenedetto@rm.unicatt.it   
Principal Investigator: Simona Di Giambenedetto, M.D.         
Clinica delle Malattie Infettive, Policlinico "Tor Vergata" Not yet recruiting
Roma, RM, Italy
Contact: Massimo Andreoni, M.D.       andreoni@uniroma2.it   
Contact: Loredana Sarmati, M.D.       sarmati@med.uniroma2.it   
Principal Investigator: Massimo Andreoni, M.D.         
Clinica delle Malattie Infettive, Ospedale Amedeo di Savoia, Università degli Studi Not yet recruiting
Torino, TO, Italy
Contact: Stefano Bonora, M.D.       stefano.bonora@unito.it   
Principal Investigator: Stefano Bonora, M.D.         
Sponsors and Collaborators
Ospedale L. Sacco – Polo Universitario
Elisa Colella, M.D.
Valentina Di Cristo, M.D.
Massimo Galli, M.D.
Investigators
Principal Investigator: Stefano - Rusconi, M.D. DIBIC "Luigi Sacco", Università degli Studi di Milano, Italy
  More Information

Publications:
Responsible Party: Stefano Rusconi, Researcher/Aggregate professor in infectious diseases, Ospedale L. Sacco - Polo Universitario
ClinicalTrials.gov Identifier: NCT01792570     History of Changes
Other Study ID Numbers: HLS03/2012
Study First Received: February 7, 2013
Last Updated: February 14, 2013
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Ospedale L. Sacco – Polo Universitario:
HIV-1
darunavir
rilpivirine
strategic study

Additional relevant MeSH terms:
HIV Seropositivity
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014