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RAltegravir Switch STudy: Effects on Endothelial Recovery (RASSTER)

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ClinicalTrials.gov Identifier: NCT01453933
Recruitment Status : Unknown
Verified December 2013 by S.F.L. van Lelyveld, UMC Utrecht.
Recruitment status was:  Recruiting
First Posted : October 18, 2011
Last Update Posted : December 18, 2013
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
S.F.L. van Lelyveld, UMC Utrecht

Study Description
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Brief Summary:
Treatment with HIV-infection with protease inhibitors is associated with high blood lipids and higher chance for cardiovascular complications. The RASSTER study aims to investigate the effect of switching the protease inhibitor lopinavir/ritonavir to raltegravir on vessel wall function and inflammation,and activation of the immune system. we hypothesize that with this intervention these parameters will improve. Since decreased vessel wall function and inflammation are initial steps in the process of atherosclerosis, it is important to know this data when treating HIV-infected patients.

Condition or disease Intervention/treatment Phase
HIV Infection Endothelial Dysfunction Drug: raltegravir Phase 4

Detailed Description:

Fixed dose combination lopinavir/ritonavir (LPV/r) is a widespread used antiretroviral drug belonging to the class of protease inhibitors (PIs). PIs are associated with an increased risk of myocardial infarction. However, data is available suggesting increased levels of plasma lipids are not the sole explanation for this observation. Treatment with LPV/r might lead to a decrease of endothelial function as well, thus explaining the increased risk of myocardial infarction besides increased plasma lipids. Raltegravir is a registered antiretroviral drug with no known cardiovascular side effects. We hypothesize that switching LPV/r to raltegravir in HIV-infected patients with suppressed plasma viral load (<50 copies/ml) will lead to an improvement of endothelial function.

Objective:

  • First, to assess the effect of the switch of lopinavir/ritonavir to raltegravir on endothelial function.
  • Second, to assess the effect of the intervention mentioned above on markers of endothelial function; immune activation; chronic inflammation; and, on plasma HIV-RNA below the cut-off of 50 copies/ml.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IV, Randomized, Open Label, Crossover, Intervention Trial to Investigate the Effect of the Switch of Lopinavir/Ritonavir to Raltegravir on Endothelial Function, Chronic Inflammation, Immune Activation and HIV Replication <50 Copies/ml
Study Start Date : January 2012
Estimated Primary Completion Date : October 2014
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Raltegravir
At baseline, lopinavir-ritonavir will be switched to raltegravir (cross-over after 8 weeks).
 Drug: raltegravir
Switch of lopinavir/ritonavir to raltegravir 400 mg BID (duration 8 weeks)
Other Name: Isentress
No Intervention: Lopinavir/ritonavir
Subjects will continue lopinavir/ritonavir (cross-over after 8 weeks)


Outcome Measures
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Primary Outcome Measures :
  1. Change in flow mediated dilatation (FMD) of the brachial artery [ Time Frame: week 8, week16 ]
    Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of raltegravir treatment as compared to the control group (treatment with lopinavir/ritonavir)


Secondary Outcome Measures :
  1. Change in markers of chronic inflammation [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ]
  2. Change in markers of immune activation [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ]
  3. Change in markers of endothelial function [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ]
  4. Changes in plasma HIV-RNA below 50 copies/ml [ Time Frame: Baseline, week 8, week 16 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • HIV-1 infection
  • Treatment with antiretroviral regimen containing lopinavir/ritonavir for at least the previous 3 months
  • No other protease inhibitors besides lopinavir/ritonavir in antiretroviral regimen
  • Subjects must have a minimum period of viral suppression (plasma HIV-RNA < 50 copies/ml) of 6 months
  • Subjects will not have a history of virological failure on antiretroviral therapy
  • Results of previous resistance testing allowing replacement of lopinavir/ritonavir by raltegravir
  • CD4+ cell count > 200 cells/µL
  • Signed informed consent

Exclusion Criteria:

  • Pregnancy
  • Breastfeeding
  • Raltegravir hypersensitivity
  • Treatment of underlying malignancy
  • Renal insufficiency requiring dialysis
  • Acute or decompensated chronic hepatitis (Child-Pugh score C)
  • Modification of antiretroviral regimen in the previous 3 months
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01453933


Contacts
Contact: Steven FL van Lelyveld, MD s.f.l.vanlelyveld@umcutrecht.nl
Contact: Andy IM Hoepelman, MD, PhD i.m.hoepelman@umcutrecht.nl

Locations
Netherlands
Onze Lieve Vrouwe Gasthuis Recruiting
Amsterdam, Noord Holland, Netherlands, 1091 AC
Contact: Guido van den Berk, MD, PhD       G.E.L.vandenBerk@olvg.nl   
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584CX
Contact: Steven FL van Lelyveld, MD       s.f.l.vanlelyveld@umcutrecht.nl   
Contact: Andy IM Hoepelman, MD, PhD       i.m.hoepelman@umcutrecht.nl   
Sub-Investigator: Steven FL van Lelyveld, MD         
Principal Investigator: Andy IM Hoepelman, MD, PhD         
Sponsors and Collaborators
UMC Utrecht
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Andy IM Hoepelman, MD University Medical Center Utrecht, The Netherlands
Study Director: Steven FL van Lelyveld, MD University Medical Center Utrecht, The Netherlands
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: S.F.L. van Lelyveld, principal investigator, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01453933     History of Changes
Other Study ID Numbers: RASSTER2010
First Posted: October 18, 2011    Key Record Dates
Last Update Posted: December 18, 2013
Last Verified: December 2013

Keywords provided by S.F.L. van Lelyveld, UMC Utrecht:
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Lopinavir/ritonavir

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