First, to assess the effect of addition of maraviroc to an abacavir-containing regimen on endothelial function; second, to assess the effect of this intervention on markers of immune activation and chronic inflammation.
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks
of treatment with maraviroc (primary endpoint)
Secondary outcome
-Change in endothelial function measured by EndoPAT
-Change in markers of chronic inflammation
-Change in markers of immune activation
-change in markers of endothelial function
-Changes in plasma HIV-RNA below 50 copies/ml
Background summary
Recent data suggest that HIV infected patients treated with abacavir might have
a higher risk for the occurrence of cardiovascular events. At time of writing
of this protocol the underlying mechanism is not yet elucidated, but some
studies suggest impaired endothelial function and elevated markers of chronic
inflammation. Recently maraviroc (Celsentri®), a CCR5-receptor antagonist,
became available for treatment of patients infected with HIV-1. On theoretical
grounds, this drug might reduce immune activation and chronic inflammation and
therefore improve endothelial function.
Study objective
First, to assess the effect of addition of maraviroc to an abacavir-containing
regimen on endothelial function; second, to assess the effect of this
intervention on markers of immune activation and chronic inflammation.
Study design
Phase IV, randomised, open label, cross-over, intervention trial.
Intervention
Randomisation into two arms: A and B. In arm A maraviroc will be added to the
abacavir-containing regimen, while study subjects in arm B will continue their
abacavir-containing regimen. After 8 weeks, cross-over of the study arms will
be performed. Subjects in arm A will then stop maraviroc, while subjects in arm
B will then start maraviroc (added to their abacavir-containig regimen during 8
weeks). The total duration of the study is 16 weeks. Maraviroc has to be taken
twice daily, dose dependent on co-medication.
Study burden and risks
Study duration is 16 weeks, consisting of 8 visits. Assuming HIV-infected
patients are monitored every three months, there will be at least 6 extra
visits. Endothelial function will be measured three times (non-invasively by
FMD- and EndoPAT measurements), each visit blood will be drawn for assessment
of the level of chronic inflammation, immune activation and virological
studies. Complete physical examination will be performed at screening visit,
during the other visits physical information will be performed on indication
only. Vital parameters and weight measurement will be performed on every visit.
In our opinion there seems minimal risk when participating in this study, since
the study medication is approved and registered, side effects (known at this
moment) are minimal, duration of treatment with study medication is short (8
weeks) and patients will be monitored frequently. With this study we hope to
gain more insight into the effect of CCR5-blockade on endothelial function, and
to learn moren on the mechanisms of endothelial dysfunction in HIV-infected
patients, especially those treated with abacavir. Finally we hope to contribute
to better treatment and prevention strategies for cardiovascular complications
in HIV-infected patients.
Heidelberglaan 100
3508 GA Utrecht
NL
Heidelberglaan 100
3508 GA Utrecht
NL
Listed location countries
Age
Inclusion criteria
-Age > 18 years
-HIV-1 infection
-Treatment with antiretroviral regimen containing abacavir for at least the previous 3 months
-Undetectable plasma HIV RNA (50 cp/ml) for at least 6 months (one *blip* allowed, which is defined as a detectable plasma HIV-RNA level between 50 and 400 copies/ml, preceded and followed by undetectable (<50 copies/ml) plasma HIV-RNA measurements)
-CD4+ cell count > 200 cells/µL
-Signed informed consent
Exclusion criteria
-Pregnancy
-Breastfeeding
-Allergy for peanuts or soya
-Hypersensitivity for maraviroc
-Treatment of underlying malignancy
-Acute infection in the preceding 30 days
-Renal insufficiency requiring hemodialysis
-Acute or decompensated chronic hepatitis
-Modification of antiretroviral regimen in the previous 3 months
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-022641-25-NL |
| CCMO | NL34314.041.10 |