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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

Tracking Information
First Submitted Date  ICMJE February 7, 2013
First Posted Date  ICMJE February 15, 2013
Last Update Posted Date April 2, 2020
Actual Study Start Date  ICMJE September 30, 2014
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2013)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DRV/r + RPV QD: Efficacy and Toxicity Reduction
Official Title  ICMJE 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.
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Human Immunodeficiency Virus
Intervention  ICMJE
  • Drug: RPV + DRV/r
    Switch to dual HAART
    Other Names:
    • RVP: rilpivirine; brand name: EdurantTM.
    • DRV: darunavir; brand name: PrezistaTM.
  • Drug: continue the PI/r-containing HAART.
    Continue the on-going triple drug HAART.
    Other Name: the drugs will depend on the successful regimen.
Study Arms  ICMJE
  • Experimental: RPV + DRV/r
    switch to RPV + DRV/r
    Intervention: Drug: RPV + DRV/r
  • Active Comparator: continue the PI/r-containing HAART.
    continue the PI/r-containing HAART
    Intervention: Drug: continue the PI/r-containing HAART.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2020)
37
Original Estimated Enrollment  ICMJE
 (submitted: February 14, 2013)
132
Actual Study Completion Date  ICMJE December 31, 2018
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01792570
Other Study ID Numbers  ICMJE HLS03/2012
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Responsible Party Stefano Rusconi, ASST Fatebenefratelli Sacco
Study Sponsor  ICMJE ASST Fatebenefratelli Sacco
Collaborators  ICMJE
  • Elisa Colella, M.D.
  • Valentina Di Cristo, M.D.
  • Massimo Galli, M.D.
Investigators  ICMJE
Principal Investigator: Stefano Rusconi, M.D. DIBIC "Luigi Sacco", Università degli Studi di Milano, Italy
PRS Account ASST Fatebenefratelli Sacco
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP