RAltegravir Switch STudy: Effects on Endothelial Recovery (RASSTER)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by UMC Utrecht
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
S.F.L. van Lelyveld, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01453933
First received: October 10, 2011
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
HIV Infection
Endothelial Dysfunction
Drug: raltegravir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • Change in flow mediated dilatation (FMD) of the brachial artery [ Time Frame: week 8, week16 ] [ Designated as safety issue: No ]
    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:
  • Change in markers of chronic inflammation [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ] [ Designated as safety issue: No ]
  • Change in markers of immune activation [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ] [ Designated as safety issue: No ]
  • Change in markers of endothelial function [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ] [ Designated as safety issue: No ]
  • Changes in plasma HIV-RNA below 50 copies/ml [ Time Frame: Baseline, week 8, week 16 ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: January 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: 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

No publications provided

Responsible Party: S.F.L. van Lelyveld, principal investigator, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01453933     History of Changes
Other Study ID Numbers: RASSTER2010
Study First Received: October 10, 2011
Last Updated: December 17, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Lopinavir/ritonavir

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
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
Lopinavir
Anti-Infective Agents
Ritonavir
Anti-Retroviral Agents
Therapeutic Uses
Pharmacologic Actions
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Antiviral Agents

ClinicalTrials.gov processed this record on July 28, 2014