Overview
- 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
- \*\Pre-treatment:\\ Imaging (CT angiography, ultrasound) to confirm eligibility.
- \\Procedure:\\ Shockwave catheter breaks up calcium, followed by stent placement.
- \\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
Description
\*\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:\\*
- \*\IVL Catheter:\\ Rapid-exchange balloon catheter with integrated electrodes generating sonic waves (80 pulses max per device).
- \\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.
Eligibility
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
