Maraviroc Abacavir STudy - Effect on Endothelial Recovery
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of maraviroc treatment as compared to the control group
研究概览
简要总结
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, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation. Recently maraviroc (Celsentri®), a CCR5-receptor antagonist, became available for treatment of patients infected with HIV-1.
Improvement of endothelial function may be a potential beneficial side effect of treatment with maraviroc, due to the potential reduction of immune activation and chronic inflammation as a result of blocking the CCR5-coreceptor. Moreover, treatment intensification of HAART with maraviroc in patients with suppressed plasma HIV_RNA may decrease plasma HIVRNA below the cut-off of 50 copies/ml as well.
The investigators hypothesize that maraviroc intensification therapy in patients on an abacavir-containing regimen will improve endothelial function.
The objectives of this study are: 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, and on plasma HIV-RNA below 50 copies/ml.
详细描述
The MASTER study is a phase IV, randomized, open label, cross-over, intervention study. Study subjects who are on stable abacavir-containing regimen will be randomized into two arms. In arm A maraviroc will be added to their regimen at baseline, 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 in subjects in arm B maraviroc will be added to their regimen (for 8 weeks again). The total duration of the study will be 16 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm A
HAART of subjects in arm A will be intensified with maraviroc during week 1-8.
干预措施: Maraviroc (Drug)
Arm B
HAART of subjects enrolled in arm B will be intensified with maraviroc during week 9-16
干预措施: Maraviroc (Drug)
结局指标
主要结局
Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of maraviroc treatment as compared to the control group
时间窗: After 8 weeks of treatment (cross-over)
次要结局
- Change in markers of immune activation(Baseline, week 2, week 4, week 8, week 10, week 12 and week 16)
- Change in endothelial function measured by EndoPAT(baseline, week 8, week 16)
- Change in markers of chronic inflammation(Baseline, week 2, week 4, week 8, week 10, week 12 and week 16)
- Change in markers of endothelial function(Baseline, week 2, week 4, week 8, week 10, week 12 and week 16)
- Changes in plasma HIV-RNA below 50 copies/ml(Baseline, week 8, week 16)
研究者
S.F.L. van Lelyveld
Coordinating investigator
UMC Utrecht