Circulating Biomarkers of Hypo-Attenuated Leaflet Thickening After Transcatheter Aortic Valve Replacement
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 6
- 主要终点
- Derivation of the panel of circulating proteins indicative of HALT
研究概览
简要总结
The purpose of the HALT Biomarkers study are to identify a panel of circulating proteins that discriminates between patients with and without Hypo-Attenuated Leaflet Thickening (HALT) and can be used to supplement the diagnosis of HALT; to characterize changes in circulating proteins after treatment of HALT with systemic anticoagulation; and to identify circulating proteins that predict the occurrence of HALT.
The study population will be adult patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) or bioprosthetic valve degeneration. Enrollment will continue until 30 patients with HALT are identified for completion of phase 1. Based on a HALT incidence rate of 10%, we anticipate enrolling 300 patients.
Patients are enrolled prior to undergoing transfemoral TAVR. Blood samples, clinical data and echocardiograms will be collected at the following timepoints: baseline (pre-TAVR, T0), post-TAVR (pre-discharge, T1), 30-day follow-up (window 3-9 weeks, T2), and 6-month follow-up (T3). Cardiac 4D CT will be performed at the 30-day follow-up visit to screen for the occurrence of HALT.
Patients with HALT will be treated with systemic anticoagulation for 5-6 months, at which point a follow-up CT scan and blood sample will be obtained. Control subjects will also undergo a 6-month study visit with blood sample collection. The study will be conducted within two phases. Phase 1 will serve as a derivation / discovery study in which candidate protein biomarkers of HALT will be identified.
Once this is successfully completed, a second cohort will be enrolled within phase 2. Phase 2 will be performed under the auspices a future contract or amendment and will seek to cross-validate the initial study findings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 65 years
- •Subject with severe native AS or severe bioprosthetic valve degeneration
- •Subject undergoing transfemoral TAVR using a Medtronic Evolut R, Evolut Pro or Evolut Pro+ transcatheter heart valve
排除标准
- •Chronic anticoagulation therapy
- •Contraindication to systemic oral anticoagulation therapy
- •Chronic kidney disease with EGFR<30 ml/min
- •Bleeding diathesis or known coagulopathy
- •Hypercoagulable state
- •Life-expectancy <12 months due to other medical conditions (e.g., malignancy, severe Alzheimer's disease, etc.)
- •The patient is currently participating in another investigational device or drug study that has not reached its primary objective/endpoint
- •Pregnant, lactating, or planning pregnancy within next 12 months
结局指标
主要结局
Derivation of the panel of circulating proteins indicative of HALT
时间窗: 6 months
1. Establish the incidence of similar proteomic profiles and the rate to which the profile occurs in TAVR recipients with HALT via a high-throughput precision proteomics platform which utilizes the proximity extension assay (PEA). PEA merges a dual-recognition antibody-based immunoassay with quantitative real-time PCR that allows for the simultaneous quantification of 92 proteins. We will focus on the 5 highest yield panels for the current investigation: cardiovascular II, cardiovascular III, cardiometabolic, inflammation, and oncology II panels. These panels will allow for the assessment of 460 circulating proteins.
Establish the rate at which these characteristics indicative of future HALT
时间窗: 6 months
Using data analysis of baseline patient characteristics to establish the rate that they are indicative of future HALT in patients with aortic stenosis. The sampling frame assumes the sequencing of 460 proteins; a 5% False Discovery Rate; a 10% prognostic prevalence; a minimum fold change of 2; and a normalization ratio of 1.
次要结局
- Cross-validation of the panel of circulating proteins indicative of HALT(6 months)
研究者
Sammy Elmariah
Director, Interventional Cardiology Research
Massachusetts General Hospital