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Kaletra in Combination With Antiretroviral Agents (PROTEKT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01076179
First received: February 24, 2010
Last updated: May 18, 2017
Last verified: May 2017
  Purpose
The purpose of this study is to investigate the tolerability of Kaletra (lopinavir/ritonavir) in combination with new substances such as integrase inhibitors (INIs), C-C chemokine receptor type 5 (CCR5) antagonists, and new non-nucleoside reverse transcriptase inhibitors (NNRTIs), as there are many reasons (intolerability, complex resistant patterns or even personal reasons) which may result in a change from the daily clinical routine and lead to the use of a newly approved antiretroviral agent in combination with Kaletra.

Condition
Human Immunodeficiency Virus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: KALETRA in Combination With New Substances (PROTEKT)

Resource links provided by NLM:


Further study details as provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):

Primary Outcome Measures:
  • Prevalence of Adverse Events (Weeks 0-144), Per Event [ Time Frame: Weeks 0 to 144 ]
    Percentage of overall number of adverse events experienced during Weeks 0-144 by adverse event type. Doctors asked participants for adverse events, grouped them into categories given in the electronic case report form (eCRF). The list of adverse events included in the eCRF were hypertriglyceridemia, hypercholesterolemia, low high density lipoprotein (HDL) cholesterol, high low density lipoprotein (LDL) cholesterol, hyperglycemia, hyperbilirubinemia, elevated aspartate aminotransferase (AST), elevated alanine aminotransferase (ALT), elevated gamma glutamyl transferase (γGT), elevated alkaline phosphatase, stomatitis, nausea, vomiting, diarrhea, abdominal pain, mood disorder, neurocerebellar disorder, headache, fatigue, fever, other (listed as 'not specified').

  • Prevalence of Adverse Events (Weeks 0-144), Per Participant [ Time Frame: Weeks 0 to 144 ]
    Percentage of participants who experienced at least 1 adverse event during Weeks 0-144 by adverse event type. Doctors asked participants for adverse events, grouped them into categories given in the eCRF. The list of adverse events included in the eCRF were hypertriglyceridemia, hypercholesterolemia, low HDL cholesterol, high LDL cholesterol, hyperglycemia, hyperbilirubinemia, elevated AST, elevated ALT, elevated γGT, elevated alkaline phosphatase, stomatitis, nausea, vomiting, diarrhea, abdominal pain, mood disorder, neurocerebellar disorder, headache, fatigue, fever, other (listed as 'not specified').


Secondary Outcome Measures:
  • Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) Cell Count [ Time Frame: Baseline (Week 0) to Week 144 ]
    Changes in participants' CD4 cell counts were assessed by measuring the change from Baseline in the number of CD4 cells at scheduled visits planned as part of routine care.

  • Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, Modified Intent-to-Treat Analysis [ Time Frame: Baseline (Week 0) to Week 144 ]
    Changes in participants' CD4 cell counts were assessed by measuring the number of CD4 cells at scheduled visits planned as part of routine care.

  • Percentage of Participants Achieving Absolute CD4 Cell Count Increases From Baseline of ≥ 100 Cells/μL at All Time Points, As Treated Analysis [ Time Frame: Baseline (Week 0) to Week 144 ]
    Changes in participants' CD4 cell counts were assessed by measuring the number of CD4 cells at scheduled visits planned as part of routine care.

  • Time to CD4 Cell Count Increase From Baseline of ≥ 100/ Cells/μL [ Time Frame: From Week 0 to Week 144 ]
  • Number of Participants With Lopinavir (LPV) Resistance at Baseline [ Time Frame: Baseline (Week 0) ]

    Characterization of baseline resistance and development of resistance using the interpretation system HIV-Genotypic Resistance-Algorithm Deutschland (GRADE; available at www.hiv-grade.de.

    Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.


  • Number of Participants With LPV Resistance During Follow-Up [ Time Frame: up to Week 144 ]
    Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.

  • Number of Participants With Protease Inhibitor (PI) Resistance at Baseline [ Time Frame: Baseline (Week 0) ]

    Characterization of baseline resistance and development of resistance using the interpretation system HIV-Genotypic Resistance-Algorithm Deutschland (GRADE; available at www.hiv-grade.de.

    Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.


  • Number of Participants With PI Resistance During Follow-Up [ Time Frame: Up to Week 144 ]
    Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.

  • Number of Participants With INI Resistance at Baseline [ Time Frame: Baseline (Week 0) ]
    Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.

  • Number of Participants With INI Resistance During Follow-Up [ Time Frame: up to Week 144 ]
    Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.

  • Number of Participants With NNRTI Resistance at Baseline [ Time Frame: Baseline (Week 0) ]
    Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.

  • Number of Participants With NNRTI Resistance During Follow-Up [ Time Frame: up to Week 144 ]
    Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.

  • Number of Participants With Nucleoside Analog Reverse-Transcriptase Inhibitor (NRTI) Resistance at Baseline [ Time Frame: Baseline (Week 0) ]
    Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.

  • Number of Participants With NRTI Resistance During Follow-Up [ Time Frame: up to Week 144 ]
    Characterization of baseline resistance and development of resistance using the interpretation system HIV-GRADE (available at www.hiv-grade.de. Genotypic interpretation was performed using the HIV-GRADE algorithm updated in December 2015). "Susceptible" indicates full susceptibility of a virus to a certain drug without any limitations in terms of resistance. "Partial" resistance is indicated if severe limitations in susceptibility have to be expected and the drug can not count for a fully active drug any more. However, these drugs can still be very useful in situations with generally limited options (salvage). "Resistant" indicates that high level drug resistance has to be expected.

  • Number of Participants With HIV-1 Coreceptor Tropism at Baseline [ Time Frame: Baseline (Week 0) ]
    Participants with CCR5 tropic virus, CXC motif chemokine receptor 4 (CRCX4) tropic virus, or dual/mixed tropic virus at Baseline.

  • Number of Participants With HIV-1 Coreceptor Tropism During Follow-up [ Time Frame: up to Week 144 ]
    Participants with CCR5 tropic virus, CXC motif chemokine receptor 4 (CRCX4) tropic virus, or dual/mixed tropic virus at Follow-up.


Other Outcome Measures:
  • Change From Baseline in HIV-1 Ribonucleic Acid (RNA) Viral Load [ Time Frame: Baseline (Week 0) to Week 144 ]
    Changes in participants' HIV-1 RNA viral load were assessed by measuring the change from Baseline at scheduled visits planned as part of routine care.

  • Time to Virologic Failure [ Time Frame: Baseline (Week 0) to Week 144 ]

    Time to virologic failure was defined by the earliest occurrence of:

    1. HIV-1 RNA > 400 copies/mL confirmed on 2 consecutive occasions after achieving at least 1 HIV-1 RNA < 50 copies/mL,
    2. HIV-1 RNA > 400 copies/mL at the final on-study visit if the participant had previously experienced at least 1 HIV-1 RNA < 50 copies/mL but subsequently did not have HIV-1 RNA > 400 copies/mL on 2 consecutive occasions, or
    3. Day 1 if the participant never achieved HIV-1 RNA < 50 copies/mL during study participation.

    A participant who prematurely discontinued study drug with HIV-1 RNA < 50 copies/mL was censored from analysis at the time of discontinuation provided that he/she did not previously experience either (a), (b) or (c).



Enrollment: 502
Study Start Date: September 2008
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Human Immunodeficiency Virus (HIV)-Infected Participants
HIV-infected participants on Kaletra and INIs or NNRTIs or CCR5 antagonists

Detailed Description:
This study was designed as a non-interventional observational study. Kaletra was prescribed in the usual manner in accordance with the terms of the local market authorization with regards to dose, population and indication as well as local guidelines.
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Community sample: HIV-positive patients
Criteria

Inclusion Criteria:

  • Patients ≥ 18years of age
  • Written informed consent (authorization to the investigator to use and/or disclose personal and/or health data before entry into the KALETRA® post marketing observational study)
  • HIV-1 infection
  • Patients treated with KALETRA®, independent from their participation in this study
  • Patients treated with novel antiretroviral therapy (for at least 8 weeks according to the study amendment), independent from their participation in this study

Exclusion Criteria:

  • Hypersensitivity against Kaletra or other ingredients or INIs or NNRTIs or CCR5 antagonists
  • Severe liver insufficiency
  • No concommitant astemizole, terfenadine, oral midazolam, triazolam, cisapride, pimozide, amiodarone, ergotamine, dihydroergotamine, ergometrine, methylergometrine, vardenafil and/or St. John's wort
  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: NCT01076179

Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Bianca Wittig, MD AbbVie Deutschland GmbH & Co. KG, Medical Department
  More Information

Additional Information:
Responsible Party: AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier: NCT01076179     History of Changes
Other Study ID Numbers: P11-021
Study First Received: February 24, 2010
Results First Received: January 18, 2017
Last Updated: May 18, 2017

Keywords provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):
Infection
Rilpivirine
CCR5 antagonists
Etravirine
Human Immunodeficiency Virus
Maraviroc
Safety and efficacy
Non nucleoside reverse transcriptase inhibitors (NNRTIs)
Integrase inhibitors
Raltegravir
Kaletra

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Lopinavir
Anti-Retroviral Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 17, 2017