NCT01792570

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Sep 2014

Typical duration for phase_3

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 7, 2013

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 15, 2013

Completed
1.6 years until next milestone

Study Start

First participant enrolled

September 30, 2014

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2018

Completed
Last Updated

April 2, 2020

Status Verified

March 1, 2020

Enrollment Period

4.3 years

First QC Date

February 7, 2013

Last Update Submit

March 31, 2020

Conditions

Human Immunodeficiency Virus

Keywords

HIV-1darunavirrilpivirinestrategic study

Outcome Measures

Primary Outcomes (1)

  • 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.

    Week 48

Secondary Outcomes (1)

  • ACTG grade III and IV events.

    over 96 weeks.

Study Arms (2)

RPV + DRV/r

EXPERIMENTAL

switch to RPV + DRV/r

Drug: RPV + DRV/r

continue the PI/r-containing HAART.

ACTIVE COMPARATOR

continue the PI/r-containing HAART

Drug: continue the PI/r-containing HAART.

Interventions

RPV + DRV/rDRUG

Switch to dual HAART

Also known as: RVP: rilpivirine; brand name: EdurantTM., DRV: darunavir; brand name: PrezistaTM.
RPV + DRV/r
continue the PI/r-containing HAART.DRUG

Continue the on-going triple drug HAART.

Also known as: the drugs will depend on the successful regimen.
continue the PI/r-containing HAART.

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Clinica delle Malattie Infettive, Policlinico Universitario

Bari, BA, Italy

Location

Divisione di Malattie Infettive, Ospedale S. Maria Annunziata, Antella

Florence, FI, Italy

Location

Clinica delle Malattie Infettive, Ospedale San Martino, Università degli Studi

Genova, GE, Italy

Location

Divisione di Malattie Infettive, Ospedale San Gerardo

Monza, MB, Italy

Location

Divisione Clinicizzata di Malattie Infettive dell'Università degli Studi, Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco"

Milan, MI, 20157, Italy

Location

I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"

Milan, MI, 20157, Italy

Location

Clinica Malattie Infettive, Policlinico Universitario

Modena, MO, Italy

Location

U.O. Malattie Infettive, Policlinico S. Matteo

Pavia, PV, Italy

Location

Clinica delle Malattie Infettive, Policlinico "Tor Vergata"

Roma, RM, Italy

Location

Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore

Roma, RM, Italy

Location

U.O. Malattie Infettive, Azienda Policlinico Umberto I, Università degli Studi "La Sapienza"

Roma, RM, Italy

Location

Clinica delle Malattie Infettive, Ospedale Amedeo di Savoia, Università degli Studi

Torino, TO, Italy

Location

Related Publications (5)

  • 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.

    PMID: 22297503BACKGROUND

  • Earley 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.

    PMID: 22312131BACKGROUND

  • Broder 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.

    PMID: 20018391BACKGROUND

  • Burgos 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.

    PMID: 22378681BACKGROUND

  • Clumeck 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.

    PMID: 21187353BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Stefano Rusconi, M.D.

    DIBIC "Luigi Sacco", Università degli Studi di Milano, Italy

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate professor in infectious diseases

Study Record Dates

First Submitted

February 7, 2013

First Posted

February 15, 2013

Study Start

September 30, 2014

Primary Completion

December 31, 2018

Study Completion

December 31, 2018

Last Updated

April 2, 2020

Record last verified: 2020-03

Data Sharing

IPD Sharing
Will share
Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR

Locations

IT(12)