RAltegravir Switch STudy: Effects on Endothelial Recovery (RASSTER)
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.
|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|
- 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)
- 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 ]
|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)|
Active Comparator: Raltegravir
At baseline, lopinavir-ritonavir will be switched to raltegravir (cross-over after 8 weeks).
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)
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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01453933
|Contact: Steven FL van Lelyveld, MDfirstname.lastname@example.org|
|Contact: Andy IM Hoepelman, MD, PhDemail@example.com|
|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 firstname.lastname@example.org|
|Contact: Andy IM Hoepelman, MD, PhD email@example.com|
|Sub-Investigator: Steven FL van Lelyveld, MD|
|Principal Investigator: Andy IM Hoepelman, MD, PhD|
|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|