A Randomized, Placebo-Controlled Mechanistic Clinical Trial of PCSK9 Inhibition With Evolocumab in Patients Undergoing Open Abdominal Aortic Aneurysm Repair
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Interleukin (IL)-6 in myeloid derived monocytes/macrophages from in AAA tissue
研究概览
简要总结
The goal of this mechanistic clinical trial is to assess whether lowering the low-density lipoprotein cholesterol (LDL-C) levels in the blood with the injections of the medication evolocumab will have any effect on the tissue or cells of patients with abdominal aortic aneurysm (AAA). Researchers will compare participants receiving evolocumab injections to participants receiving placebo injections to see how the tissue and cells of the aorta are affected by changes in LDL-C levels.
详细描述
After being informed about the study and its potential risks, all patients giving informed consent will undergo a baseline visit and be randomized to received either evolocumab 140mg subcutaneously or placebo. This baseline visit includes a vital signs assessment, laboratory tests, medical history and medication review, a pregnancy test (if applicable), and training on how to perform drug injections. Participants will receive 3 doses/autoinjectors of study drug or placebo and be instructed to perform injections every 14 days starting 5 weeks prior to their scheduled AAA repair. If the baseline assessment occurs 5 weeks prior to their scheduled AAA, the first injection will be performed during this visit. Participants will have the option of coming back to the site for injections 2 and 3 or perform these injections at home under telehealth supervision. At the time of open AAA repair, participants will repeat laboratory tests and have a sample of aneurysm tissue taken. Participants will then have a follow up phone call 4 weeks after AAA repair to assess for any adverse events. At the conclusion of the study investigators will examine gene expression and protein levels in the aortic tissue to determine the impact of LDL-C lowering with evolocumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Abdominal aortic aneurysm (AAA) requiring open surgical repair
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
排除标准
- •Prior use of a PCSK9 inhibitor (evolocumab, alirocumab, inclisiran) within 6 months of the baseline visit
- •LDL-C < 40 mg/dL (within 3 months of baseline visit)
- •Known allergy to PCSK9 inhibitor
- •Aortic dissection
- •Vascular connective tissue disorders
- •Type I-III or V Thoraco-abdominal Aortic Aneurysm
- •Vasculitis or inflammatory aneurysm
- •Pregnant or lactating women
- •Poorly controlled diabetes (A1C > 10%)
- •Chronic kidney disease Stage 4/5 or End Stage Renal Disease (ESRD) on hemodialysis (HD)
- •Liver Disease (alanine transaminase [ALT] or aspartate aminotransferase [ALT] > 3.0 x upper limits of normal) (within 3 months of baseline visit)
- •Known latex or naturally rubber allergy
- •Treatment with another investigational product within 30 days or 5 half-lives of the investigation drug before consent (whichever is longer) that would have an impact on endpoints associated with this trial.
- •Any other condition that the Investigator feels prohibits participants' ability to comply with study or follow up.
研究组 & 干预措施
Evolocumab
Evolocumab is the drug that will be administered in this study. It will be administered as a 140mg subcutaneous injection every 14 days for 5 weeks (for a total of 3 doses).
干预措施: Evolocumab (Drug)
Placebo
This arm is a matching placebo that will be administered in the same fashion as the study drug if the patient is randomized to placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Interleukin (IL)-6 in myeloid derived monocytes/macrophages from in AAA tissue
时间窗: AAA Repair (Week 5)
IL-6 expression will be measured in myeloid cells in the aortic tissue specimens using single nucleus RNA sequencing and confirmed by whole tissue ELISA.
次要结局
- Infiltrating immune cell composition and their activation/inflammatory states in AAA tissue(AAA Repair (Week 5))
- Matrix metalloproteinase (MMP)-9 in myeloid derived monocytes/macrophages from in AAA tissue(AAA Repair (Week 5))
- Smooth muscle composition of AAA tissue(AAA Repair (Week 5))
研究者
Scott Damrauer
Associate Professor of Surgery
University of Pennsylvania