HIV InfectionPhase 4RASSTERNCT01453933
RAltegravir Switch STudy: Effects on Endothelial Recovery
A Phase 4 study testing raltegravir in people with HIV Infection and Endothelial Dysfunction, run by UMC Utrecht at 2 sites in Netherlands.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection, Endothelial Dysfunction
- What is being tested?
- raltegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesNetherlands
- Study dates
- Jan 2012to Dec 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Results of previous resistance testing allowing replacement of lopinavir/ritonavir by raltegravir
- CD4+ cell count > 200 cells/µL
- Signed informed consent
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Steven FL van Lelyveld, MD contact
Andy IM Hoepelman, MD, PhD contact
Netherlands2 sites, 2 recruiting
- Recruiting
Onze Lieve Vrouwe Gasthuis
Amsterdam, North Holland, 1091 AC
Guido van den Berk, MD, PhD, G.E.L.vandenBerk@olvg.nl
- Recruiting
University Medical Center Utrecht
Utrecht, 3584CX
Steven FL van Lelyveld, MD, s.f.l.vanlelyveld@umcutrecht.nl
Andy IM Hoepelman, MD, PhD, i.m.hoepelman@umcutrecht.nl
About this study
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
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.
Read the 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.
- Conditions
- HIV Infection, Endothelial Dysfunction
- Being tested
- raltegravir
- Keywords
- Anti-HIV Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents, Lopinavir/ritonavir
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
raltegravirDrug
Also called Isentress
Switch of lopinavir/ritonavir to raltegravir 400 mg BID (duration 8 weeks)
| Study group | Role | What they receive |
|---|---|---|
| Raltegravir | Active comparator | At baseline, lopinavir-ritonavir will be switched to raltegravir (cross-over after 8 weeks). Receives: Drug: raltegravir |
| Lopinavir/ritonavir | No intervention | Subjects will continue lopinavir/ritonavir (cross-over after 8 weeks) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: week 8, week16
Secondary outcomes (4)
Change in markers of chronic inflammation
Measured: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16
Change in markers of immune activation
Measured: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16
Change in markers of endothelial function
Measured: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16
Changes in plasma HIV-RNA below 50 copies/ml
Measured: Baseline, week 8, week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2011 (estimated)
- Study startJan 2012
- Primary completionOct 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, S.F.L. van Lelyveld, UMC Utrecht
- Investigators
- Andy IM Hoepelman, MD, Principal investigator, University Medical Center Utrecht, The NetherlandsSteven FL van Lelyveld, MD, Study director, University Medical Center Utrecht, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01453933
- Sponsor's protocol ID
- RASSTER2010
- Acronym
- RASSTER
- Status last verified
- Dec 2013
- First submitted
- 10 Oct 2011
- Last updated
- 18 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Krikke M, Tesselaar K, van den Berk GEL, Otto SA, Freriks LH, van Lelyveld SFL, Visseren FJL, Hoepelman AIM, Arends JE. The effect of switching protease inhibitors to raltegravir on endothelial function, in HIV-infected patients. HIV Clin Trials. 2018 Apr;19(2):75-83. doi: 10.1080/15284336.2018.1455366.
PubMed 29770748
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01453933
- Acronym / sponsor ID
- RASSTER / RASSTER2010
- Conditions
- HIV Infection, Endothelial Dysfunction
- Keywords
- Anti-HIV Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents, Lopinavir/ritonavir
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Jan 2012
- Primary completion
- Oct 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 18 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Raltegravir | Active comparator | Drug: raltegravirAt baseline, lopinavir-ritonavir will be switched to raltegravir (cross-over after 8 weeks). |
| Lopinavir/ritonavir | No intervention | –Subjects will continue lopinavir/ritonavir (cross-over after 8 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (7 listed)
- Pregnancy
- Breastfeeding
- Raltegravir hypersensitivity
- Treatment of underlying malignancy
- Renal insufficiency requiring dialysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| raltegravirAlso: IsentressSwitch of lopinavir/ritonavir to raltegravir 400 mg BID (duration 8 weeks) | Drug | Raltegravir |
Primary outcome
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)
4 secondary outcomes
Change in markers of chronic inflammation
Time frame: 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
Change in markers of endothelial function
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2013.
- Derived from this study: PubMed 29770748Krikke M, Tesselaar K, van den Berk GEL, Otto SA, Freriks LH, van Lelyveld SFL, Visseren FJL, Hoepelman AIM, Arends JE. The effect of switching protease inhibitors to raltegravir on endothelial function, in HIV-infected patients. HIV Clin Trials. 2018 Apr;19(2):75-83. doi: 10.1080/15284336.2018.1455366.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven FL van Lelyveld, MD contact
Andy IM Hoepelman, MD, PhD contact
Andy IM Hoepelman, MD principal investigator
University Medical Center Utrecht, The Netherlands
Steven FL van Lelyveld, MD study director
University Medical Center Utrecht, The Netherlands
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing raltegravir in people with HIV Infection and Endothelial Dysfunction, run by UMC Utrecht at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Steven FL van Lelyveld, MD (s.f.l.vanlelyveld@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in flow mediated dilatation (FMD) of the brachial artery (time frame: week 8, week16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01453933, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2013.