Switch to Darunavir/r + Maraviroc Quaque Die in Patients With R5 Tropism by Viral DNA Genotyping (GUSTA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Catholic University of the Sacred Heart
Sponsor:
Information provided by (Responsible Party):
Simona Di Giambenedetto, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier:
NCT01367210
First received: June 3, 2011
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

Objectives of the study:

  1. To verify the safety and the efficacy of the study treatment, defined as the persistent control of the virus' replication at 48 weeks after the simplification to maraviroc + darunavir with ritonavir in patients with R5 tropism by viral DNA genotyping.
  2. To collect relevant information about the safety, the immunologic and the economic impact of this strategy.

Condition Intervention Phase
HIV Infection
Drug: Maraviroc, Darunavir/r
Drug: current antiretroviral therapy with 3 drugs
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Switch to Darunavir/r + Maraviroc QD in Patients With R5 Tropism by Viral DNA Genotyping With Suppressed Viremia (GUSTA): a Multicenter, Open-label, Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Catholic University of the Sacred Heart:

Primary Outcome Measures:
  • proportion of patients with virological failure (two consecutive measures of HIV-RNA higher than 50 copies/mL or a single measure higher than 1000 copies/mL) within 48 weeks at per protocol analysis, with switch=failure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • proportion of patients with virological failure (two consecutive measures of HIV-RNA higher than 50 copies/mL or a single measure higher than 1000 copies/mL) within 96 weeks at intention-to treat analysis with missing value=Failure [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Time to virological failure at survival analysis [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients with at failure X4 tropism viral tropism (RNA or DNA genotyping) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Evolution of CD4 cell- cluster of differentiation 4 cell count during the 96 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Evolution of adherence and quality of life after 24, 48 and 96 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Evolution of maraviroc, darunavir, ritonavir plasma concentrations during the 96 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • Evolution of metabolic parameters at 96 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Change of the results of neurocognitive tests at 48 and 96 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Modification of bone density and subcutaneous fat at 48 and 96 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Modification of Intima-Media Thickness and Flow Mediated Dilation at 48 and 96 weeks [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Economic impact of Darunavir/ritonavir+ Maraviroc versus Highly Active Antiretroviral Therapy [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 330
Study Start Date: June 2011
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MARAVIROC, DARUNAVIR/r
Treatment simplification from a "standard" combined antiretroviral therapy including 3 drugs to Maraviroc plus Darunavir with Ritonavir. Treatment simplification from three-drugs- to two-drugs-based antiretroviral therapy
Drug: Maraviroc, Darunavir/r
Maraviroc 300 mg Darunavir 800 mg Ritonavir 100 mg
Sham Comparator: current ART with 3 drugs
Patients on HAART with three drugs and HIV RNA below 50 copies/mL
Drug: current antiretroviral therapy with 3 drugs
To continue the assumption of previous HAART

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients treated with the same regimen including 3 HAART from at least 4 months
  • Aged 18 years or older
  • Who gave informed consent to the participation to the study
  • With at least two viral load < 50 copies/mL in two consecutive determinations at least 6 months apart (tolerance of two weeks)
  • With CD4 cell count > 200 cells/μL and absence of any opportunistic infection or AIDS-related disease for at least one year prior to the screening.
  • With R5 tropism by viral DNA genotyping (geno2pheno "clonal")
  • With CD4 cell count nadir>50 cell/mmc or 100 cell/mmc if previous enfuvirtide or integrase inhibitors use

Exclusion Criteria:

  • With at least one major or two minor mutation conferring resistance to darunavir reported in the update list of International AIDS Society - USA , in previous resistance test
  • Previous D/M or X4 viral tropism
  • Previous major clinical toxicities (grade >=3) to the proposed drugs of the study
  • Pregnancy or breast feeding, desire of pregnancy in the short term
  • Past exposure to Chemokine Receptor 5 antagonist
  • HBsAg serostatus
  • Liver cirrhosis of class C (Child-Pugh)
  • Sulpha drug hypersensitivity
  • The presence of major non AIDS-defining diseases that, in the opinion of the investigator, may compromise the retention of the patient in the study for the necessary follow-up period.
  • Estimated glomerular filtration < 30 ml/min (cockroft-Gaut; MDRD formula if black-African or african-american) at screening visit
  • Hypertransaminasemia of grade IV (more than 10 times the upper normal limit) at screening visit
  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: NCT01367210

Contacts
Contact: Andrea De Luca, Prof 00390630154945 andrea.deluca@rm.unicatt.it
Contact: Manuela Colafigli, MD 00390630155366 manuela76@inwind.it

Locations
Italy
Catholic University of Sacred Heart Recruiting
Rome, Italy, 00168
Contact: Andrea De Luca, MD    00390630154945    andrea.deluca@rm.unicatt.it   
Sub-Investigator: Manuela Colafigli, MD         
Sub-Investigator: Massimiliano Fabbiani, MD         
Sponsors and Collaborators
Catholic University of the Sacred Heart
Investigators
Principal Investigator: Andrea De Luca, Prof Catholic University of the Sacred Heart
  More Information

No publications provided

Responsible Party: Simona Di Giambenedetto, Dr, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier: NCT01367210     History of Changes
Other Study ID Numbers: 2010-023316-13
Study First Received: June 3, 2011
Last Updated: July 30, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Catholic University of the Sacred Heart:
HIV
AIDS
Highly Active AntiRetroviral Therapy
Simplification
Maraviroc
Darunavir
Treatment experienced
Tropism

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus 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 September 29, 2014