RAltegravir Switch STudy: Effects on Endothelial Recovery (RASSTER)

December 17, 2013 updated by: S.F.L. van Lelyveld, UMC Utrecht

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Utrecht, Netherlands, 3584CX
    • Noord Holland
      • Amsterdam, Noord Holland, Netherlands, 1091 AC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Isentress
No Intervention: Lopinavir/ritonavir
Subjects will continue lopinavir/ritonavir (cross-over after 8 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
week 8, week16

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UMC Utrecht

Collaborators

Merck Sharp & Dohme LLC

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Anticipated)

October 1, 2014

Study Completion (Anticipated)

December 1, 2014

Study Registration Dates

First Submitted

October 10, 2011

First Submitted That Met QC Criteria

October 13, 2011

First Posted (Estimate)

October 18, 2011

Study Record Updates

Last Update Posted (Estimate)

December 18, 2013

Last Update Submitted That Met QC Criteria

December 17, 2013

Last Verified

December 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RASSTER2010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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