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

October 10, 2011
December 17, 2013
January 2012
October 2014   (final data collection date for primary outcome measure)
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)
Same as current
Complete list of historical versions of study NCT01453933 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change in markers of chronic inflammation [ Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16 ] [ Designated as safety issue: No ]
  • Change in markers of immune activation [ Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16 ] [ Designated as safety issue: No ]
  • Change in markers of endothelial function [ Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, 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 ]
Not Provided
Not Provided
 
RAltegravir Switch STudy: Effects on Endothelial Recovery
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

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.

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.
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infection
  • Endothelial Dysfunction
Drug: raltegravir
Switch of lopinavir/ritonavir to raltegravir 400 mg BID (duration 8 weeks)
Other Name: Isentress
  • Active Comparator: Raltegravir
    At baseline, lopinavir-ritonavir will be switched to raltegravir (cross-over after 8 weeks).
    Intervention: Drug: raltegravir
  • No Intervention: Lopinavir/ritonavir
    Subjects will continue lopinavir/ritonavir (cross-over after 8 weeks)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
24
December 2014
October 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Steven FL van Lelyveld, MD s.f.l.vanlelyveld@umcutrecht.nl
Contact: Andy IM Hoepelman, MD, PhD i.m.hoepelman@umcutrecht.nl
Netherlands
 
NCT01453933
RASSTER2010
No
S.F.L. van Lelyveld, UMC Utrecht
UMC Utrecht
Merck Sharp & Dohme Corp.
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
UMC Utrecht
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP