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

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Fundacion SEIMC-GESIDA
ClinicalTrials.gov Identifier:
NCT00865475
First received: March 18, 2009
Last updated: September 11, 2013
Last verified: September 2013
  Purpose

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


Condition Intervention Phase
HIV Infection
HIV Infections
Drug: AZT+3TC+ABV (Trizivir)
Drug: Switching to LPV/r monotherapy (Kaletra)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Fundacion SEIMC-GESIDA:

Primary Outcome Measures:
  • Limb Fat changes measured by DEXA [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 20 % loss peripheral fat measured by DEXA [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Perception of change on body fat by physician and patient. [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Lipohypertrophy [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 38
Study Start Date: December 2008
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • AZT+3TC+ABV (Trizivir)
  • 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 Name: Kaletra

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.

  Eligibility

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

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.
  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: NCT00865475

Locations
Spain
Hospital Ntra.Sra. de Zumarraga
Zumarraga, Guipuzcua, Spain, 28700
Hospital Severo Ochoa
Leganes, Madrid, Spain, 28911
Hospital de Donostia
Donostia, San Sebastian, Spain, 20014
Hospital de Basurto
Bilbao, Vizcaya, Spain, 48013
Hospital La Paz
Madrid, Spain, 28046
Hospital Doce de Octubre
Madrid, Spain, 28041
H. Son Dureta
Mallorca, Spain
Sponsors and Collaborators
Fundacion SEIMC-GESIDA
Abbott
Investigators
Study Chair: Jose Antonio Iribarren Hospital de Donostia
  More Information

No publications provided

Responsible Party: Fundacion SEIMC-GESIDA
ClinicalTrials.gov Identifier: NCT00865475     History of Changes
Other Study ID Numbers: GESIDA 6108, 2008-003438-12, 6108
Study First Received: March 18, 2009
Last Updated: September 11, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Fundacion SEIMC-GESIDA:
HIV infection
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lipodystrophy
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
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Lamivudine
Lopinavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014