Kaletra in Combination With Antiretroviral Agents (PROTEKT)

• ClinicalTrials.gov Identifier: NCT01076179
• Recruitment Status: Completed
• First Posted: February 26, 2010
• Results First Posted: May 19, 2017
• Last Update Posted: May 19, 2017
• Sponsor: AbbVie (prior sponsor, Abbott)
• Information provided by (Responsible Party): AbbVie ( AbbVie (prior sponsor, Abbott) )

Study Description

Brief Summary:

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 or disease
Human Immunodeficiency Virus

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 502 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: KALETRA in Combination With New Substances (PROTEKT)
• Study Start Date: September 2008
• Actual Primary Completion Date: January 2016
• Actual Study Completion Date: January 2016

Groups and Cohorts

Group/Cohort
Human Immunodeficiency Virus (HIV)-Infected Participants; HIV-infected participants on Kaletra and INIs or NNRTIs or CCR5 antagonists

Outcome Measures

Primary Outcome Measures :

1. 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').
2. 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 :

1. 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.
2. 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.
3. 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.
4. Time to CD4 Cell Count Increase From Baseline of ≥ 100/ Cells/μL [ Time Frame: From Week 0 to Week 144 ]
5. 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.

6. 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.
7. 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.

8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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:

1. 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.
2. 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• 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

Sponsors and Collaborators

AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: Bianca Wittig, MD; AbbVie Deutschland GmbH & Co. KG, Medical Department

More Information

Additional Information:

Related Info 

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01076179
• Other Study ID Numbers: P11-021
• First Posted: February 26, 2010
• Results First Posted: May 19, 2017
• Last Update Posted: May 19, 2017
• Last Verified: May 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:

Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Slow Virus Diseases