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

Официальное название

A Prospective, Multicenter, Single-Arm Objective Performance Criteria Clinical Trial Evaluating the Safety and Efficacy of a Single-Use Neurovascular Intravascular Shockwave Catheter and Intravascular Shockwave Therapy Device for Pretreatment of Calcified Lesions in the Extracranial Carotid Artery (CREATE Trial)）

Обзор

* Clinical Trial Summary * Trial Title:\*\* CREATE Trial: Safety and Efficacy of IVL for Carotid Calcified Lesions * Sponsor:\*\* Shanghai Bluesail Boyuan Medical Technology Co., Ltd. * Clinical Trial Leader:\*\* Beijing Anzhen Hospital * Coordinating Investigator:\*\* Prof. Huo Xiaochuan * Study Purpose This trial assesses a new device-a single-use neurovascular intravascular shockwave catheter and therapy device-for treating calcified blockages in the carotid artery. It uses sound waves to break up calcium deposits, facilitating stent placement and blood flow restoration. * Eligibility * Adults aged 18-80 with severe carotid artery narrowing (≥50% symptomatic or ≥70% asymptomatic) due to calcium buildup. * Patients who failed standard balloon dilation. * Exclusions include pregnancy, recent strokes/heart attacks, uncontrolled hypertension, or other high-risk conditions. * Study Design * \*\*Type:\*\* Prospective, multicenter, single-arm trial. * \*\*Sample Size:\*\* 204 patients across multiple hospitals. * \*\*Duration:\*\* 1-month follow-up post-procedure. * Procedures 1. \*\*Pre-treatment:\*\* Imaging (CT angiography, ultrasound) to confirm eligibility. 2. \*\*Procedure:\*\* Shockwave catheter breaks up calcium, followed by stent placement. 3. \*\*Follow-up:\*\* Assessments at 7 days (or discharge) and 1 month post-procedure. * Benefits and Risks * \*\*Benefits:\*\* Improved stent placement success, reduced risk of complications, minimally invasive with shorter recovery time. * \*\*Risks:\*\* Bleeding, infection, vessel damage, stroke, heart attack, device malfunction. Risks are closely monitored with emergency protocols. * Patient Protections * Ethics committee approval and strict safety guidelines. * Voluntary participation with the option to withdraw anytime. * Free treatment and compensation for trial-related injuries. * For Healthcare Providers * \*\*Innovation:\*\* Adapts coronary lithotripsy technology for carotid use. * \*\*Evidence:\*\* Supported by preclinical data and a pilot study (100% success rate in 5 patients). * \*\*Endpoints:\*\* Primary: Stent success (residual stenosis \<30%) and 30-day major adverse events. Secondary: Device success rate, repeat procedures, long-term outcomes. * Contact Information For questions, contact: \*\*Ms. Zhang Yanjiao\*\* Email: yanjiao.zhang@jwmsgrp.com

Подробное описание

\*\*Detailed Clinical Trial Description\*\*

\### \*\*1. Background and Rationale\*\* \*\*Clinical Need:\*\*

* \*\*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.

\### \*\*2. Study Objectives\*\* \*\*Primary Objectives:\*\* * \*\*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).

\### \*\*3. Methodology\*\* \*\*Study Design:\*\* * \*\*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).

\### \*\*5. Risk Management\*\* \*\*Anticipated Risks:\*\* * \*\*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).

\### \*\*6. Statistical Plan\*\* \*\*Sample Size Justification:\*\* * \*\*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).

\### \*\*7. Ethical and Regulatory Compliance\*\* * \*\*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).

\### \*\*8. Operational Oversight\*\* * \*\*Monitoring:\*\* Centralized EDC (Medidata Rave) with 100% source data verification. * \*\*Audits:\*\* Independent DSMB reviews safety data biannually.

Вмешательства

• Устройство Neurovascular Intravascular Shockwave Catheter
  Device: Neurovascular Intravascular Shockwave Catheter (single-use, rapid-exchange balloon catheter with integrated shockwave emitters). Intravascular Shockwave Therapy Device (IVL-HVG-N01, generates localized shockwaves to fracture calcifications). Procedure: Patients undergo standard CAS preparation with guidewire placement and cerebral protection. If conventional balloon angioplasty fails (residual stenosis \>70%), the IVL catheter is advanced to the target lesion. Shockwave therapy is

Первичные конечные точки

• Procedural Success Rate [Срок оценки: Immediately post-procedure (intraoperative).]
• 30-Day Major Adverse Events (MAE) Rate [Срок оценки: 30 days (±7 days) post-procedure.]

Вторичные конечные точки (5)

• Device Success [Срок оценки: Intraoperative]
• Device Malfunction Rate [Срок оценки: Intraoperative]
• Target Lesion Revascularization Rate [Срок оценки: Within 7 days/Before Discharge, 1 Month Postoperative]
• Ipsilateral Stroke Rate [Срок оценки: Within 7 days/Before Discharge, 1 Month Postoperative]
• Major Adverse Cardio-Cerebrovascular Events (MACCE) Rate [Срок оценки: Within 7 days/Before Discharge, 1 Month Postoperative]

Критерии участия

Критерии включения

• Age 18-80 years (inclusive), gender unrestricted.
• Extracranial carotid artery: Preoperative CT angiography (CTA) confirms symptomatic carotid stenosis ≥50% or asymptomatic carotid stenosis ≥70% with calcification (CTA measurement: calcification > 50% of circumference).

Note: (Extracranial carotid artery: Internal carotid artery or carotid bifurcation; Symptomatic refers to having had a non-disabling ischemic stroke or TIA within 6 months.)

• Intraoperative digital subtraction angiography (DSA) confirms carotid stenosis ≥50% (by NASCET criteria) or asymptomatic carotid stenosis ≥70% (by NASCET criteria).
• Participants with a pre-enrollment modified Rankin Scale (mRS) score ≤2.
• Participants planned for carotid artery stenting (CAS) who have failed conventional balloon dilation.
• Patients or their legal guardians understand the purpose of the trial, provide informed consent, and agree to follow-up.

Критерии исключения

• Target lesion caused by non-atherosclerotic disease.
• Participants with complete occlusion of the target lesion or contralateral carotid artery.
• Participants with severe disability due to cerebral infarction.
• Participants with large acute or subacute thrombi near the target lesion, or with arteriovenous malformations or aneurysms.
• Participants with tortuous target lesion vessels that prevent stent placement.
• Participants with symptomatic severe stenosis in other cerebral vessels.
• Participants requiring concurrent or additional surgical interventions during the trial period.
• Participants with tandem severe stenosis or occlusion in vessels proximal or distal to the target lesion.
• Participants who have had a myocardial infarction or large cerebral infarction within 2 weeks prior to screening.
• Participants who have had intracranial hemorrhage within 3 months prior to screening.
• Participants with vulnerable or high-risk plaques (unstable, prone to rupture, and thrombosis leading to acute cardiovascular events or death) as judged by carotid ultrasound.
• Participants with uncontrolled hypertension (systolic blood pressure persistently ≥180 mmHg or diastolic blood pressure persistently ≥110 mmHg).
• Participants with known platelet count < 90×10\^9/L, severe liver impairment (transaminases > 3 times the upper limit of normal), severe renal impairment (serum creatinine > 2.5 mg/dL \[221 µmol/L\]), or New York Heart Association Class IV heart failure.
• Participants with coagulopathy (INR ≥2.0) or contraindications to heparin or antiplatelet agents.
• Participants with active infections.
• Participants unable to use cerebral protection devices.
• Participants allergic to components of the investigational device or contrast agents (excluding rash).
• Participants with life expectancy less than 1 year.
• Pregnant or breastfeeding women.
• Participants currently enrolled in another drug or medical device clinical trial (before reaching the primary endpoint).
• Other situations where the investigator deems the participant unsuitable for the trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing An Zhen Hospital of the Capital University of Medical Sciences — Пекин

Идентификаторы

NCT: NCT06936176 · LFBY-202501

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗