Prevention of Lipoatrophy in Patients Treated With Lopinavir/Ritonavir in Monotherapy Versus ZDV + 3TC + ABC (KALIPO)

September 11, 2013 updated by: Fundacion SEIMC-GESIDA

A Randomized Comparative Clinical Trial of ZDV + 3TC + ABC (Trizivir) vs Monotherapy With Lopinavir/R (Kaletra) in Patients With Viral Suppression on Previous Treatment With ZDV + 3TC + ABC (Trizivir) for Preventing Lipoatrophy

The aim of this study is to measure the prevention of lipoatrophy in patients treated with Lopinavir/R in monotherapy versus ZDV + 3TC + ABC

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In recent years mayor progress has been made in therapeutic approaches with the introduction of HAART, which has meant a huge fall in morbidity-mortality in Western countries.

However, despite having a variety of potent HAART combinations, some patients do not obtain adequate suppression. The causes of virological failure are complex, and one of the most significant factors is the incomplete compliance with the prescribed dosage of highly-active antiretroviral therapy (HAART). The development of fixed dose combination products is most commonly used to help simplify the dosages and improve treatment compliance.

One of the main problems associated with the treatment of HIV infection is the change in body structure, generally grouped under the term of lipodystrophy. These usually include fat accumulation in the stomach, or abdominal girth, and, even worse, atrophy in the face, arms, and legs. It is usually associated with metabolic disorders, with increased levels of triglycerides, cholesterol and/or insulin resistance.

The incidence of lipodystrophy increases progressively over time in patients starting treatment with antiretroviral agents. It is estimated that, after 2 years of treatment, 20%-30% of patients experience moderate or severe lipodystrophy.

Trizivir® is a combination of three antiretroviral agents: Abacavir, Lamivudine and Zidovudine in a tablet. All of them belong to the group of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs.

The main advantage of Trizivir is the possibility of simplifying antiretroviral treatment. Multiple studies have been performed showing that simplification of HAART with Trizivir enhances compliance and improves quality of life in patients maintaining the efficacy of previous antiretroviral treatments.

Kaletra® (lopinavir+ritonavir) is a combination of two protease inhibitors: lopinavir plus a low dose of ritonavir, enhancing the action of the former.

Previous studies have shown that most patients treated with Kaletra monotherapy have an undetectable viral load after 48 weeks. Monotherapy failures were not associated with the development of primary resistance mutations.

To date the development of lipoatrophy appears to occur more frequently in patients with a NRTI- containing regimen. The combination of abacavir, zidovudine and lamivudine has been investigated in patients naive to antiretroviral treatments and in patients already treated with NRTIs.

In this setting, we designed this clinical trial to establish the potential benefit of Kaletra in monotherapy for the prevention of lipoatrophy. For this purpose, we will compare keeping on treatment with TZV in patients with viral suppression vs switching to Kaletra in monotherapy in order to prevent fat changes.

Since the purpose of the study is to establish the ability of Kaletra to prevent the development of and exclude patients with acute intolerance to Kaletra, the patients assigned to the experimental group will be treated for 4 weeks with Trizivir and Kaletra before switching to Kaletra monotherapy.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 4

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

  • Spain
      • Madrid, Spain, 28046
        • Hospital La Paz
      • Madrid, Spain, 28041
        • Hospital Doce de Octubre
      • Mallorca, Spain
        • H. Son Dureta
    • Guipuzcua
      • Zumarraga, Guipuzcua, Spain, 28700
        • Hospital Ntra.Sra. de Zumarraga
    • Madrid
      • Leganes, Madrid, Spain, 28911
        • Hospital Severo Ochoa
    • San Sebastian
      • Donostia, San Sebastian, Spain, 20014
        • Hospital de Donostia
    • Vizcaya
      • Bilbao, Vizcaya, Spain, 48013
        • Hospital de Basurto

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:

  • Patients infected with HIV 1 documented by positive HIV 1 antibody test and/or positive PCR test confirmed for HIV 1 RNA.
  • Patients on treatment with Trizivir with an undetectable viral burden defined as < 50 copies/ml in the past 6 months.
  • Men or women aged ≥ 18 years.
  • CD4 cell count ≥ 200 cells/μl.
  • For women of child bearing age, a negative urine pregnancy test at the screening visit.
  • Patients giving their written informed consent before completing any study specific screening procedure.

Exclusion Criteria:

  • Patients with previously failed therapy with protease inhibitors (PI) or those receiving sub optimum therapy with nucleoside analogue reverse transcriptase inhibitors (NRTI) for the study disease.
  • Presence of lipoatrophy defined by the investigator (any grade) or by the patient (in this case, at least two sites of mild degree or one of at least moderate degree).
  • Known history of drug addiction or chronic use of alcohol that, in the investigator's opinion, contraindicates participation in the study.
  • Pregnant or nursing women or women of child bearing age not using an adequate contraceptive method according to the investigator's criterion.
  • Current active opportunistic infection or documented infection in the 4 weeks prior to screening.
  • Renal disease with creatinine clearance < 50 ml/min.
  • Concomitant use of nephrotoxic or immunosuppressive agents.
  • Patient currently treated with systemic corticosteroids, interleukine 2, or chemotherapy.
  • Patients treated with other investigational agents.
  • Patients with acute hepatitis.
  • Any disease that, at the criterion in the investigator, contraindicates the patient's participation in the study.

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: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: TZV (Trizivir)
Keeping on TZV in patients with viral suppression
EXPERIMENTAL: 2
Switching to LPV/r monotherapy
Drug: AZT+3TC+ABV (Trizivir)
Patients on treatment with TZV and viral suppression will be randomized to keep on TZV vs switching to LPV/r monotherapy
Other Names:
  • LPV/r (Kaletra)
Drug: Switching to LPV/r monotherapy (Kaletra)
Patients on AZT+3TC+ABV with viral suppression will be randomized to keep on vs switching to LPV/r
Other Names:
  • Kaletra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Limb Fat changes measured by DEXA
Time Frame: 48 weeks
48 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
20 % loss peripheral fat measured by DEXA
Time Frame: 96 weeks
96 weeks
Perception of change on body fat by physician and patient.
Time Frame: 96 weeks
96 weeks
Lipohypertrophy
Time Frame: 96 weeks
96 weeks

Collaborators and Investigators

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

Sponsor

Fundacion SEIMC-GESIDA

Collaborators

Abbott

Investigators

  • Study Chair: Jose Antonio Iribarren, Hospital de Donostia

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

December 1, 2008

Primary Completion (ACTUAL)

March 1, 2013

Study Completion (ACTUAL)

March 1, 2013

Study Registration Dates

First Submitted

March 18, 2009

First Submitted That Met QC Criteria

March 18, 2009

First Posted (ESTIMATE)

March 19, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

September 12, 2013

Last Update Submitted That Met QC Criteria

September 11, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GESIDA 6108
  • 2008-003438-12 (EUDRACT_NUMBER)
  • 6108 (OTHER: GESIDA)

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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