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.