\*\*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.
