Raltegravir Switch for Toxicity or Adverse Events - Full Text View

Purpose

This study aims to verify the persistent control of the virus replication at 48 weeks after the simplification to tenofovir + emtricitabine + raltegravir or to lamivudine+abacavir+raltegravir in patients with optimal virological suppression without any virological failure to previous combined antiretroviral therapies needing a therapeutic switch for toxicity related issues or adverse events.

Condition	Intervention	Phase
HIV/AIDS Antiretroviral Therapy HIV Infections	Drug: tenofovir emtricitabine raltegravir Drug: Lamivudine Abacavir Raltegravir Drug: Abacavir free	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase IIb Pilot Study for the Evaluation of the Safety and the Feasibility of Treatment Simplification to Tenofovir+Emtricitabine+Raltegravir or to Lamivudine+Abacavir+Raltegravir in Patients With Optimal Virological Control and Toxicity to the Current Combined Antiretroviral Regimen

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Lamivudine Abacavir Emtricitabine Tenofovir Abacavir sulfate Tenofovir Disoproxil Fumarate Raltegravir Raltegravir potassium

U.S. FDA Resources

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

Primary Outcome Measures:

To verify the persistent control of the virus replication after the simplification to tenofovir+emtricitabine+raltegravir or to lamivudine+abacavir+raltegravir in patients with optimal virological suppression without any previous virological failure [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to virological failure (two consecutive HIV-RNA levels > 50 copies/mL or a single value >1000 copies/mL) at survival analysis [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Proportion of patients with viral load lower than 50 copies/mL at 48 weeks at the intention to treat analysis [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Evolution of CD4 cell count during the 48 weeks of study [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Evolution of adherence and quality of life during the 48 weeks of study [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Evolution of raltegravir plasma concentrations during the 48 weeks of study [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Evolution of metabolic parameters during the 48 weeks of study [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Change of the results of neurocognitive tests at 48 weeks of study [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Change of bone density and of adipose tissue by DEXA analysis at 48 weeks of study [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]


Enrollment:	40
Study Start Date:	August 2009
Study Completion Date:	December 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Tenofovir Emtricitabine Raltegravir Patients switching to raltegravir with tenofovir+emtricitabine as backbone	Drug: tenofovir emtricitabine raltegravir switch from current antiretroviral regimen to raltegravir with tenofovir/emtricitabine as backbone
Experimental: Lamivudine Abacavir Raltegravir Switch from current antiretroviral regimen to raltegravir with abacavir/lamivudine as backbone	Drug: Lamivudine Abacavir Raltegravir Switch from current antiretroviral regimen to raltegravir with abacavir/lamivudine as backbone
Experimental: Abacavir free Patients switched to raltegravir whose backbone therapy should not be randomized in order to avoid the use of abacavir (HLA-B*5701 positive patients,Framingham score 20% or higher)	Drug: Abacavir free Patients will receive raltegravir with tenofovir/emtricitabine; data will be added to those of Tenofovir Emtricitabine Raltegravir arm in a separate longitudinal analysis comparing data at baseline and at 48 weeks. In this separate analysis, data will not be compared to those obtained from the Lamivudine Abacavir Raltegravir arm. The number of patients in this arm is not pre-established.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients treated with a combined antiretroviral therapy from at least 1 year
Aged 18 years or older
With one or more of the following conditions:
- Grade 3 or 4 Dyslipidemia
- Any Hyperglycemia
- Lipodystrophy (patient's self report, confirmed by physician's physical examination)
- Moderate/severe cardiovascular risk, defined as a calcium score higher than 40 or a Framingham score higher than 10 (estimated 10 years cardiovascular risk: 10%)
- Diarrhea (at least 3 emissions of loose stool every day for at least 3 days every week)
With at least two HIV-RNA levels <50 copies/mL on two consecutive determinations at least 3 months apart
With CD4 cell count >200 cells/ μL for at least 6 months and absence of any opportunistic infection or AIDS-related disease during the last year before screening.
Who gave informed consent to the participation to the study

Exclusion Criteria:

Pregnancy or breast feeding, desire of pregnancy in the short term
Previous virological failure (two consecutive HIV-RNA levels > 50 copies/mL or a single value >1000 copies/mL) to antiretroviral therapy and/or previous exposure to mono- or dual therapies with reverse transcriptase nucleoside analogues except for patients with subsequent genotypic resistance tests showing no resistance mutations to any of the study drugs.
Previous exposure to inhibitors of HIV-1 integrase
Previous major toxicity to any of the study drugs
Spontaneous treatment interruptions in disagreement with the treating physician in the last year or loss to follow-up for at least 6 months, at least once in the last two years
Current alcohol or drug abuse or any other condition which, in the judgment of the treating physician, may impair the patient's adherence to the new drug regimen and/or to the protocol's procedures
Patients with grade 3 or 4 laboratory abnormalities at screening (except for lipid and glucose levels)

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: NCT00958100

Locations


Italy
Policlinico A. Gemelli
Rome, Italy, 00168

Sponsors and Collaborators

Catholic University of the Sacred Heart

More Information


Responsible Party:	Simona Di Giambenedetto, Dr, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier:	NCT00958100 History of Changes
Other Study ID Numbers:	2009−014316−35
Study First Received:	August 12, 2009
Last Updated:	February 3, 2015
Health Authority:	Italy: The Italian Medicines Agency

Keywords provided by Catholic University of the Sacred Heart:


raltegravir switch toxicity treatment experienced

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Tenofovir Raltegravir Potassium Emtricitabine Lamivudine	Abacavir Dideoxynucleosides Antiviral Agents Anti-Infective Agents Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents HIV Integrase Inhibitors Integrase Inhibitors Antimetabolites

ClinicalTrials.gov processed this record on September 23, 2016

Raltegravir Switch for Toxicity or Adverse Events (RaSTA)