RAltegravir Switch STudy: Effects on Endothelial Recovery

HIV Infection Clinical Trial

— RASSTER  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01453933
• Other study ID #: RASSTER2010
• Status: Recruiting
• Phase: Phase 4
• First received: October 10, 2011
• Last updated: December 17, 2013
• Start date: January 2012
• Est. completion date: December 2014

Study information

• Verified date: December 2013
• Source: UMC Utrecht
• Contact: Steven FL van Lelyveld, MD
• Email: s.f.l.vanlelyveld[@]umcutrecht.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endothelial Dysfunction
• HIV Infection

Intervention

Drug:
• raltegravir
Switch of lopinavir/ritonavir to raltegravir 400 mg BID (duration 8 weeks)

Locations

Country	Name	City	State
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam	Noord Holland
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in flow mediated dilatation (FMD) of the brachial artery	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)	week 8, week16	No
Secondary	Change in markers of chronic inflammation		Baseline, week 2, week 4, week 8, week 10, week 12 and week 16	No
Secondary	Change in markers of immune activation		Baseline, week 2, week 4, week 8, week 10, week 12 and week 16	No
Secondary	Change in markers of endothelial function		Baseline, week 2, week 4, week 8, week 10, week 12 and week 16	No
Secondary	Changes in plasma HIV-RNA below 50 copies/ml		Baseline, week 8, week 16	No