A Limited-Center, Prospective, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Cenicriviroc Mesylate on Arterial Inflammation in People Living With HIV
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 19
- 主要终点
- Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel.
研究概览
简要总结
The study was conducted to determine if cenicriviroc mesylate (CVC) would decrease vascular inflammation as measured by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging of the aorta and carotid arteries.
详细描述
This was a double-blind, placebo-controlled phase II clinical trial comparing the intervention of CVC versus placebo for a duration of 24 weeks on arterial inflammation evaluated by FDG-PET/CT imaging.
A total of 110 participants were randomized 2:1 to the CVC arm (Arm A) or placebo for CVC arm (Arm B). Stratification by statin use at randomization ensured even distribution of statin use between the treatment groups.
Analyses were based on the efficacy population: all enrolled participants who completed at least 22 weeks of study treatment and remained on the same ART drug class throughout the study without use of prohibited medications.
Analysis of the primary outcome utilized multiple imputation by regression to impute missing data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented to be living with HIV-1 infection.
- •Currently on a stable, continuous NNRTI-based or unboosted INSTI-based ART regimen for ≥48 weeks prior to study entry with no plans to change ART during the course of the study.
- •At least a year of controlled HIV-1 RNA levels.
- •Current CD4+ cell count >200 cells/mm^
- •Elevated cardiovascular risk defined as at least one of the following:
- •Clinical atherosclerotic disease (symptomatic atherosclerotic lesions in any vessel)
- •Subclinical atherosclerotic disease (coronary artery calcification [CAC] >10 or presence of non-obstructive plaques)
- •Diabetes mellitus (DM) or prediabetes
- •Hypertension or blood pressure ≥130/80 mmHg
- •Elevated LDL cholesterol (fasting LDL of >160 mg/dL)
- •Low HDL cholesterol (<40 mg/dL)
- •Current tobacco smoking
- •Family history of premature coronary artery disease (CAD)
- •hsCRP >2.0 mg/L
排除标准
- •Acute coronary syndrome
- •A current diagnosis of latent or active tuberculosis (TB) infection
- •Current diagnosis with other intracellular pathogens (Mycobacterium avium complex, Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans).
- •Untreated hepatitis B virus (HBV) infection
- •Current hepatitis C virus (HCV) infection
- •Current, acute or clinically significant infection or illness requiring IV antibiotics or hospitalization
- •History of cirrhosis with severe hepatic impairment and/or hepatic decompensation
- •Active malignancy, except squamous cell skin cancer.
- •Hemoglobin A1c >8% within 90 days prior to study entry.
- •Initiation of statin therapy or change in statin dose within 90 days prior to study entry.
- •Current use of any of the statins at the doses indicated:
- •Atorvastatin, >40 mg/day dose
- •Rosuvastatin, ≥20 mg/day dose
- •Concurrent use of drugs with potential drug-drug interactions with CVC within 90 days prior to study entry.
研究组 & 干预措施
CVC arm (Arm A)
Participants with pre-existing ART regimen of efavirenz (EFV) took CVC 300 mg. Participants with all other pre-existing ART regimens took CVC 150 mg.
干预措施: CVC 150 mg (Drug)
CVC arm (Arm A)
Participants with pre-existing ART regimen of efavirenz (EFV) took CVC 300 mg. Participants with all other pre-existing ART regimens took CVC 150 mg.
干预措施: CVC 300 mg (Drug)
Placebo for CVC arm (Arm B)
Participants with pre-existing ART regimen of efavirenz (EFV) took placebo for CVC 300 mg. Participants with all other pre-existing ART regimens took placebo for CVC 150 mg.
干预措施: Placebo for CVC 150 mg (Other)
Placebo for CVC arm (Arm B)
Participants with pre-existing ART regimen of efavirenz (EFV) took placebo for CVC 300 mg. Participants with all other pre-existing ART regimens took placebo for CVC 150 mg.
干预措施: Placebo for CVC 300 mg (Other)
结局指标
主要结局
Change (Expressed as Ratio to Baseline) in 18-FDG-PET Target-to-background Ratio (TBR) of the Most Diseased Segment (MDS) of the Index (Most-inflamed) Vessel.
时间窗: Measured at baseline and week 24
Target-to-Background Ratio (TBR) measures the intensity of inflammation of a target arterial wall (aorta, left carotid, right carotid), relative to its respective blood background. Specifically, it is the ratio of the Standardized Uptake Value (SUV) of 18-FDG-PET in the target vessel to SUV in the blood background. A negative number for the change in TBR means a reduction in the target arterial wall inflammation over time. Index vessel is the vessel with the highest vessel TBR at baseline. The most diseased segment is the approximately 1-cm section of the vessel with the highest activity at baseline. The results are expressed as the ratio of TBR at week 24 to baseline. For the statistical analyses, results for the 6 and 9 missing values in Arm A and Arm B, respectively, were imputed using multiple imputation by regression.
次要结局
- Change (Expressed as Ratio to Baseline) in Aortic TBR (and Other TBRs)(Measured at baseline and week 24)
- Change (Expressed as Ratio to Baseline) in Standardized Uptake Value (SUV) Measured in the Carotid Arteries and Aorta(Measured at baseline and week 24)
- Change in Fasting Glucose(Measured at baseline and week 24)
- Change (Expressed as Ratio to Baseline) in Fasting Insulin and Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR)(Measured at baseline and week 24)
- Change (Expressed as Ratio to Baseline) in Biomarkers of Inflammation (IL-6, hsCRP, and MCP-1)(Measured at baseline and week 24)
- Change in Biomarkers of Immune Activation (sCD14 and sCD163)(Measured at baseline and week 24)
- Change (Expressed as Ratio to Baseline) in Plasma Levels of Chemokine Receptor 5 (CCR5) Ligands (RANTES and MIP-1 Beta)(Measured at baseline and week 24)