DRV/r + RPV QD: Efficacy and Toxicity Reduction

March 31, 2020 updated by: Stefano Rusconi, ASST Fatebenefratelli Sacco

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • BA
      • Bari, BA, Italy
        • Clinica delle Malattie Infettive, Policlinico Universitario
    • FI
      • Firenze, FI, Italy
        • Divisione di Malattie Infettive, Ospedale S. Maria Annunziata, Antella
    • GE
      • Genova, GE, Italy
        • Clinica delle Malattie Infettive, Ospedale San Martino, Università degli Studi
    • MB
      • Monza, MB, Italy
        • Divisione di Malattie Infettive, Ospedale San Gerardo
    • MI
      • Milano, MI, Italy, 20157
        • 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"
    • MO
      • Modena, MO, Italy
        • Clinica Malattie Infettive, Policlinico Universitario
    • PV
      • Pavia, PV, Italy
        • U.O. Malattie Infettive, Policlinico S. Matteo
    • RM
      • Roma, RM, 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"
    • TO
      • Torino, TO, Italy
        • Clinica delle Malattie Infettive, Ospedale Amedeo di Savoia, Università degli Studi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • the drugs will depend on the successful regimen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
over 96 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ASST Fatebenefratelli Sacco

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2014

Primary Completion (Actual)

December 31, 2018

Study Completion (Actual)

December 31, 2018

Study Registration Dates

First Submitted

February 7, 2013

First Submitted That Met QC Criteria

February 14, 2013

First Posted (Estimate)

February 15, 2013

Study Record Updates

Last Update Posted (Actual)

April 2, 2020

Last Update Submitted That Met QC Criteria

March 31, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HLS03/2012

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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