Jud. Cluj, Mun. Cluj-napoca, Romania

Xeltis Peripheral Artery Disease (XPAD) Bypass Conduit Early Feasibility Study

Genetic Risk Stratification for Primary Prevention of CAD in Men and Pre & Post-menopausal Women

Coronary artery disease (CAD) is an epidemic, being the most common cause of death in the world. CAD is preventable as shown by clinical trials that reduce conventional risk factors such as hypercholesterolemia. Epidemiologists have claimed 40-60% of pre-disposition to CAD is genetic. In 2007, the investigators and the Icelandic group independently identified the first genetic risk variant for CAD, 9p21. Through the formation of an international consortium, the investigators have now identified over 200 genetic risk variants predisposing to CAD. Utilizing a genetic risk score (GRS) based on these variants for CAD, several studies have retrospectively documented the risk stratification for primary or secondary prevention of CAD to be superior and relatively independent of, conventional risk factors. Studies in over 1 million individuals show those with the highest genetic risk exhibit up to a 4-fold increased risk of CAD. More importantly, those with a high GRS and a more favorable lifestyle experienced 50% reduction in cardiac events. In the high risk group one needs to treat only 13 individuals with statin therapy to prevent one cardiac event. The GRS detects those at high risk who will benefit most from primary prevention. The myth that one cannot treat genetic predisposition has been dispelled. While secondary prevention of CAD has been successful, application of primary prevention has until now lacked a risk marker to detect those who would benefit most. Given only 47% of the population will experience a cardiac event, administering preventive therapy, such as statin, to everyone would be unnecessarily expensive and inappropriate. Since the GRS is determined at birth, and does not change during one lifetime it is close to ideal for primary prevention. GRS detects among asymptomatic individuals at any age those at high-risk for CAD, who will benefit most from preventive therapy. The investigators propose to genotype males and females at age 40 years and older, who are asymptomatic and without known heart disease (N=2000). DNA from a blood sample will be genotyped for millions of genetic risk variants for CAD by Baylor College of Medicine Human Genome Sequencing Center Clinical Laboratory (HGSC-CL) in CLIA-approved laboratories. The derived GRS will be added to the conventional risk score using the American College of Cardiology/American Heart Association's (AHA) Pooled Cohort Atherosclerotic Cardiovascular Disease (ASCVD) Risk Equation. In the female cohort, investigators will also be screening for female-specific risk factors that have been added to the ACC/AHA 2018 Blood Cholesterol Guidelines to be used as risk enhancers. Everyone at high risk, will be referred to their physician for further management and given the opportunity for genetic counseling by a member of the research team. Completion of the 2 year recruitment will meet the objectives, however, an annual follow-up will be obtained by electronic survey via REDCap, letter or phone call over a 10 year period as it may provide information on long term genetic prediction. The overall objective after 2 years is to determine if genetic screening for risk of CAD in asymptomatic men and women has the discriminatory power to detect those at highest risk who would potentially benefit most from appropriate primary prevention. It will also determine whether the GRS is appropriate for different ethnic and race groups such as Hispanics, African Americans and Whites, and to what extent those individuals knowing that they are at higher risk, are more likely to seek further advice on management of the risks (either through changes in lifestyle or therapy). The investigators expect to complete recruitment in two years and prove that the GRS is appropriate for clinical application and can detect individuals that have a 50% or more increase in risk for CAD.

Study of Percutaneous Coronary Intervention in Left Main Coronary Artery Disease in Patients With Acute Coronary Syndrome at Sohag University Hospitals

Efficacy and Safety Study of Endovascular Treatment of Asymptomatic Carotid Artery Stenosis

This multicenter, prospective, open-label, randomized controlled trial with blinded endpoint assessment aims to evaluate the safety and efficacy of endovascular stenting combined with best medical therapy (BMT) versus BMT alone in patients with asymptomatic severe stenosis (70-99%) of the internal carotid artery (ICA). The study will enroll 982 participants aged 40-80 years who have no history of ipsilateral transient ischemic attack (TIA), stroke, or related neurological symptoms within the past 6 months and have declined carotid endarterectomy. The primary objective is to determine whether stenting reduces the composite risk of stroke, myocardial infarction, or death within 30 days post-procedure/enrollment, as well as ipsilateral stroke from 30 days to 1 year. Secondary objectives include assessing procedural success, restenosis rates, cognitive outcomes (measured by Montreal Cognitive Assessment [MoCA] and Mini-Mental State Examination [MMSE]), and long-term clinical outcomes. The trial will be conducted across multiple centers in China, led by Beijing Tiantan Hospital, Capital Medical University. Participants will be randomly assigned (1:1) via a computer-generated stratified randomization scheme to either the intervention group (endovascular stenting plus BMT) or the control group (BMT alone). BMT includes antiplatelet therapy, lipid-lowering agents, blood pressure control, and management of other cardiocerebrovascular risk factors. Endpoint adjudication will be performed by an independent blinded clinical events committee to minimize bias. Eligible participants must have severe ICA origin stenosis confirmed by ultrasound, computed tomography angiography (CTA), or digital subtraction angiography (DSA), with contralateral ICA stenosis <70%. Key exclusion criteria include recent symptomatic stenosis, intracranial hemorrhage within 1 year, severe cardiopulmonary comorbidities, contraindications to antiplatelet/anticoagulant therapy, life expectancy <5 years, or anatomical challenges (e.g., Type III aortic arch, severe vascular tortuosity/calcification). Imaging exclusions focus on technical feasibility and safety, such as tandem intracranial stenosis or distal lesions more severe than the target stenosis. The primary endpoints are the 30-day composite rate of stroke, myocardial infarction, or death, and the incidence of ipsilateral stroke between 30 days and 1 year. Secondary endpoints include technical success (defined as residual stenosis <30% with Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow post-procedure), 30-day and 12-month mortality, restenosis rates, and cognitive changes. Statistical analysis will follow the intention-to-treat principle, with Kaplan-Meier survival analysis and log-rank tests for primary outcomes. Cox proportional hazards models will estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses will use per-protocol and as-treated populations. The study duration is scheduled from August 2024 to July 2028, including a 12-month follow-up period. Ethical approval will be obtained from all participating centers, and the trial will adhere to the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines.

The Management of Asymptomatic Carotid Stenosis

Prospective Trial of IVL for Calcified Carotid Lesions(CREATE Trial)(Extended Follow-Up)

This clinical trial evaluates the safety and long-term efficacy of a disposable neurovascular intravascular lithotripsy (IVL) catheter and intravascular lithotripsy treatment device for pre-treatment of calcified lesions in the extracranial segment of the carotid artery. The study is designed as a prospective, multicenter, single-arm trial （extended follow-up period）. All patients participating in this extended follow-up period are sourced from the registered clinical trial.（The registered clinical trial:Participants aged 18-80 years with symptomatic (≥50%) or asymptomatic (≥70%) calcified carotid artery stenosis confirmed by CT angiography (CTA) and digital subtraction angiography (DSA) are eligible. Patients who have failed conventional balloon dilation and are planned for carotid artery stenting (CAS) will be included.） - Endpoints: - **Primary Endpoint**: Surgical success rate defined as residual stenosis <30% after stenting. - **Secondary Endpoints**: Target lesion re-narrowing rate, target lesion revascularization rate, MAE (major adverse events) rate, ipsilateral stroke rate, and MACCE (major adverse cardiovascular and cerebrovascular events) rate at 3 and 6 months postoperatively. - Ethical Considerations: Informed consent will be obtained from all participants or their legal guardians. The study will be conducted in accordance with the Helsinki Declaration and local regulatory requirements.

Prospective Trial of IVL for Calcified Carotid Lesions(CREATE Trial)

**Detailed Clinical Trial Description** - **Carotid artery calcification** is a major contributor to ischemic stroke, accounting for 15-20% of cases. Severe calcification complicates stent placement, leading to high rates of residual stenosis and adverse events (e.g., stroke, myocardial infarction) with conventional treatments like balloon angioplasty. - **Current Limitations:** Standard therapies often fail to adequately modify calcified plaques, necessitating high-pressure balloon dilation, which risks embolization, vessel dissection, or hemodynamic instability. **Innovative Solution:** - The **intravascular lithotripsy (IVL) system** delivers localized sonic pressure waves to fracture calcium deposits while sparing soft tissue, enabling safer stent deployment. - **Evidence Base:** Supported by coronary IVL trials (e.g., DISRUPT CAD I-IV) and off-label carotid case reports demonstrating 90-100% technical success with minimal complications. - **Efficacy:** Assess **surgical success rate** (stent placement with residual stenosis <30%). - **Safety:** Evaluate **30-day major adverse events (MAE)** (composite of death, stroke, or myocardial infarction). **Secondary Objectives:** - Device success rate (successful delivery/retrieval of IVL catheter). - Rates of target lesion revascularization, ipsilateral stroke, and MACCE (major adverse cardiac/cerebrovascular events). - **Prospective, multicenter, single-arm, objective performance criteria (OPC) trial.** - **No control group** due to ethical concerns (standard therapy failure is an inclusion criterion). **Intervention:** 1. **IVL Catheter:** Rapid-exchange balloon catheter with integrated electrodes generating sonic waves (80 pulses max per device). 2. **IVL Device:** Console delivering controlled energy pulses (compatible with 3.0-5.0 mm balloons). **Procedure Steps:** - **Pre-treatment:** Dual antiplatelet therapy (aspirin + clopidogrel) for ≥3 days. - **IVL Delivery:** - Balloon inflation to 6 atm, followed by 10 pulses/cycle (up to 8 cycles). - Stent placement post-calcium modification. - **Post-procedure:** Monitoring for MAE at 7 days and 1 month. **Key Assessments:** - **Imaging:** CT angiography (baseline), DSA (intraoperative), ultrasound (follow-up). - **Clinical:** NIHSS/mRS scores, vital signs, lab tests (hematology, biochemistry). - **4. Participant Selection** **Inclusion Criteria:** - Symptomatic (≥50%) or asymptomatic (≥70%) carotid stenosis with circumferential calcium >50% (CTA-confirmed). - Failed conventional balloon pre-dilation (residual stenosis >70%). - Modified Rankin Scale (mRS) score ≤2. **Exclusion Criteria:** - Vulnerable plaques, recent stroke/MI (within 2-12 weeks), or contraindications to antiplatelets. - Severe comorbidities (e.g., NYHA Class IV heart failure, creatinine >2.5 mg/dL). - **Procedure-related:** Vessel dissection (1-3%), embolic stroke (2-5%), access-site hematoma. - **Device-related:** Balloon rupture, electrode malfunction (<1%). **Mitigation Strategies:** - **Embolic protection devices** mandatory. - **Strict operator training** (≥5 supervised cases required). - **Real-time monitoring** for hemodynamic instability (bradycardia/hypotension). - **Efficacy endpoint:** 107 patients needed (95% expected vs. 85% OPC, α=0.025, power=90%). - **Safety endpoint:** 204 patients (4.5% expected vs. 11% OPC). - **Total:** 204 (accounting for 10% dropout). **Analysis Populations:** - **Full Analysis Set (FAS):** All treated patients (intent-to-treat). - **Per-Protocol Set (PPS):** Excludes major protocol deviations. **Statistical Tests:** - Primary endpoints: **One-sided 95% CI** (success rate lower bound >85%; MAE upper bound <11%). - Secondary endpoints: Descriptive statistics (rates, Kaplan-Meier survival analysis). - **Ethics Approval:** Obtained from all site IRBs (reference: LFBY-202501). - **Informed Consent:** Mandatory, with provisions for legally authorized representatives. - **Data Protection:** Compliant with China's Personal Information Protection Law (PIPL). - **Monitoring:** Centralized EDC (Medidata Rave) with 100% source data verification. - **Audits:** Independent DSMB reviews safety data biannually.

Gao's Triple Eversion Carotid Endarterectomy

The investigators retrospectively reviewed the charts of patients who underwent GTE-CEA performed by the same group of vascular surgeons since 17 September, 2021. Patients who did not meet the diagnostic criteria for carotid artery stenosis (CAS); those with asymptomatic CAS < 50%, preoperatively confirmed by digital subtraction angiography (DSA) or computed tomography angiography (CTA); and those with stenosis at the opening of the common carotid artery (CCA) were excluded from our study.

Study on the Trans-Carotid Artery Occlusion Shunt System Combined With Introducer Sets

The physician shall strictly follow the clinical study protocol and shall not deviate from or substantially change the protocol. However, in case of emergency such as immediate risk to the subjects, which needs tobe eliminated immediately, it may be reported in written form afterwards. During the course of the study,documents such as amendments to the clinical study protocol and informed consent, requests for deviation,and resumption of the suspended clinical study shall be subject to the written approval of the Ethics Committee