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Switching From Protease Inhibitor (PI) to Etravirine in HIV-1 Infected Subjects With Viremia Suppression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dra. EUGENIA NEGREDO PUIGMAL, Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier:
NCT01034917
First received: December 17, 2009
Last updated: October 24, 2012
Last verified: July 2012
History of Changes
  Purpose

This is a 48 week randomized, prospective, controlled, open-label, proof-of-concept pilot clinical trial.

Patients with HIV-1 infection on HAART PI-based regimen will be randomized to switch from the PI to etravirine (400 mg dissolved in water every 24 hours) or to continue with the same approach.

The aim of the study is to compare the virological efficacy of the etravirine-based regimen with standard PI-containing regimen.


Condition Intervention Phase
HIV
 Drug: Etravirine 400 mg dissolved in water every 24 hours
Drug: Continue with the same antiretroviral regimen
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study to Assess the Efficacy and Safety of Switching Protease Inhibitor to Etravirine in HIV-1-infected Subjects With Viremia Suppression

Resource links provided by NLM:

Drug Information available for: Etravirine
U.S. FDA Resources

Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • Viral load [ Time Frame: week 48 after baseline ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • CD4+/CD8+ T lymphocytes count [ Time Frame: evolution from baseline to week 48 ] [ Designated as safety issue: No ]
  • Genotypic test [ Time Frame: if virologic failure occurs ] [ Designated as safety issue: No ]
  • Lipid profile: total, HDL-, LDL-cholesterol and triglyceride levels [ Time Frame: evolution from baseline to week 48 ] [ Designated as safety issue: No ]
  • Administration of lipid-lowering drugs throughout the study [ Time Frame: from baseline to week 48 ] [ Designated as safety issue: No ]
  • Cardiovascular risk assessed by the SCORE equation [ Time Frame: evolution from baseline to week 48 ] [ Designated as safety issue: No ]
  • Patient's satisfaction assessed by 2 scales of type Likert [ Time Frame: evolution from baseline to week 48 ] [ Designated as safety issue: No ]
  • Adverse events related to antiretroviral treatment [ Time Frame: from baseline to week 48 ] [ Designated as safety issue: No ]
  • Etravirine plasma trough concentration [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]

Enrollment: 43
Study Start Date: December 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etravirine group
To switch from the PI to Etravirine 400 mg dissolved in water every 24 hours
 Drug: Etravirine 400 mg dissolved in water every 24 hours
Switch from the PI to Etravirine 400 mg dissolved in water every 24 hours
Other Name: ETV
Active Comparator: Control group
Continue with the same antiretroviral regimen
 Drug: Continue with the same antiretroviral regimen
Continue with the same antiretroviral regimen
Other Name: CNT

Detailed Description:

Etravirine is a second generation non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) approved by the U.S. Food and Drug Administration (FDA) in January 2008 and by the European Medicines Agency in September 2008 for clinical use in adults with incomplete virologic suppression and resistance to previous NNRTI and other antiretroviral classes.

A question that has not been explored is whether subjects with sustained undetectable HIV-1 RNA-levels experiencing antiretroviral-related toxicity can safely switch their current PI to etravirine. This treatment strategy could allow improvements in tolerability and lipid profile and would permit an easy posology (400 mg dissolved in water every 24 hours). We designed a proof-of-concept study to test the efficacy and safety of switching from a Protease Inhibitor (PI) to etravirine in subjects with viral suppression as an antiretroviral strategy of simplification therapy, based on the high antiviral potency, low toxicity, together with its easy posology (in water dissolution).

Patients with HIV-1 infection on HAART PI-based regimen will be randomized to switch from the PI to etravirine (400 mg dissolved in water every 24 hours) or to continue with the same approach.

The primary endpoint would be the percentage of patients who maintain virological suppression at week 48.

  Eligibility

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

Inclusion Criteria:

  1. Adult patient having a diagnosis of HIV-1 infection.
  2. Antiretroviral therapy started at least 12 months before, always with a HAART combination including 2 NRTIs plus a PI.
  3. Maintained undetectable plasma HIV-1 RNA (VL < 50 copies/mL) since the beginning of antiretroviral therapy, for at least 6 months.
  4. Absence of suspected or documented resistance mutations in the RT associated to NNRTIs or to any NRTI.

  5. Patient having at least one of the following conditions:

    • Dyslipemia (LDL cholesterol >130 mg/dL or triglycerides > 350 mg/dL) derived from their current PI regimen or current use of lipid-lowering agents due to dyslipemia,
    • Antiretroviral-related gastrointestinal disturbances, or
    • Low patient's satisfaction associated with the current regimen posology (BID regimen, ritonavir use, ritonavir intolerance…).
  6. Good treatment adherence.
  7. Voluntary written informed consent.

Exclusion Criteria:

  1. Previous therapy with mono or dual antiretroviral therapies after initial of HAART era.
  2. Previous antiretroviral treatment failures, treatment interruptions (A) or blips (B) in viral load (VL > 50 copies/mL).
  3. Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion.
  4. Pregnancy or fertile women willing to be pregnant.
  5. Clinically significant malabsorption syndrome within 30 days prior to randomization.

(A) Patients who in the past made any interruption of treatment (provide that it has not been in the last year) may be considered candidates for the study, if they meet other criteria for inclusion, since the break in the treatment should not assume the emergence of mutations.

(B) Small blips that are preceded or forwarded by 2 undetectable viral loads will not be taken in care.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01034917

Locations
Spain
Germans Trias i Pujol University Hospital
Badalona, Barcelona, Spain, 08916
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Investigators
Principal Investigator: Eugenia Negredo, MD,PhD Fundacio Lluita Contra la SIDA
  More Information

No publications provided

Responsible Party: Dra. EUGENIA NEGREDO PUIGMAL, Dra. Eugenia Negredo Puigmal, Fundacio Lluita Contra la SIDA
ClinicalTrials.gov Identifier: NCT01034917     History of Changes
Other Study ID Numbers: ETRA-SWITCH
Study First Received: December 17, 2009
Last Updated: October 24, 2012
Health Authority: Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:
Active Comparator
Placebo Comparator
Sham Comparator
 No intervention
Other
Treatment Experienced

Additional relevant MeSH terms:
Viremia
Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
 Pathologic Processes
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013