Mechanical Thrombectomy for Acute Pulmonary Embolism

Overview

Research Objective: To prospectively compare the efficacy and safety of a pre-collaboratively developed ultra-thin PTFE minimally invasive thrombectomy system versus standard pharmacological therapy in patients with acute pulmonary embolism (PE), both administered on top of standard care. Research Content: Patients meeting all the following criteria will be enrolled: Aged 18-75 years (male or female) Clinically diagnosed with acute PE Right ventricular/left ventricular diameter ratio (RV/LV) ≥0.9 on computed tomographic pulmonary angiography (CTPA) Provision of voluntary written informed consent. Study Design: After confirming eligibility, subjects will be randomized at a 1:1 ratio into two groups: Innovative Device Group: Minimally invasive thrombectomy Standard Pharmacological Therapy Group: Pharmacological thrombolysis + anticoagulation Study Endpoints: Primary Efficacy Endpoint: Reduction in RV/LV ratio (measured by CTPA) from baseline to 48 hours post-treatment. Primary Safety Endpoint: Incidence of Major Adverse Events (MAEs) from baseline to 48 hours post-treatment, defined as: Procedure-related death Major bleeding (per VARC-2 criteria: life-threatening, disabling, or major bleeding) Treatment-related clinical deterioration, including: Unplanned mechanical ventilation Arterial hypotension (systolic blood pressure \<90 mmHg for \>1 hour or requiring vasopressors) or shock Cardiopulmonary resuscitation Sustained deterioration in oxygenation Emergency surgical embolectomy. Key Terminology Notes: RV/LV: Right Ventricular/Left Ventricular diameter ratio (standard medical abbreviation retained). VARC-2: Valve Academic Research Consortium-2 (internationally recognized bleeding criteria). PTFE: Polytetrafluoroethylene (material name preserved). MAE: Major Adverse Events (acronym defined at first use). Clinical deterioration: Explicitly specified with objective clinical indicators. This translation maintains scientific precision while adhering to international clinical trial reporting standards (ICH-GCP). The structure aligns with typical English-language study protocols for clarity and reproducibility.

1. Research Objective To prospectively evaluate the comparative efficacy and safety of a novel ultra-thin polytetrafluoroethylene (PTFE) minimally invasive thrombectomy system versus guideline-directed pharmacological thrombolysis in patients with acute intermediate-high-risk pulmonary embolism (PE), both administered as adjuncts to standard anticoagulation therapy. 2. Study Population Inclusion Criteria: Adults aged 18-75 years (all genders) Acute PE confirmed by computed tomographic pulmonary angiography (CTPA) within 14 days of symptom onset Right ventricular dysfunction defined as RV/LV diameter ratio ≥0.9 on baseline CTPA Provision of written informed consent Exclusion Criteria: Absolute contraindications to thrombolysis (e.g., active bleeding, recent intracranial hemorrhage, major surgery within 14 days) Hemodynamic instability requiring immediate rescue therapy (systolic BP \<90 mmHg with end-organ hypoperfusion) Severe renal impairment (eGFR \<30 mL/min/1.73m²) or hepatic failure (Child-Pugh Class C) Life expectancy \<6 months due to non-PE comorbidities 3. Study Design Design: Prospective, multicenter, open-label, randomized controlled trial with blinded endpoint adjudication Randomization: Eligible subjects stratified by PE severity (RV/LV: 0.9-1.0 vs. \>1.0) and thrombus burden (main/lobar vs. segmental PA involvement), then randomized 1:1 via centralized web-based system. Intervention Groups: Group A (Innovative Device): Ultra-thin PTFE thrombectomy catheter deployed under fluoroscopic guidance via femoral access Procedure completion within 90 minutes; mandatory peri-procedural unfractionated heparin (target ACT 250-300 s) Post-procedure: Enoxaparin 1 mg/kg BID → transitioned to rivaroxaban 20 mg OD at 24 hours Group B (Standard Therapy): Alteplase infusion: 10 mg bolus + 90 mg over 2 hours (max 100 mg) Concurrent heparin infusion (target aPTT 60-80 s) → switched to rivaroxaban 15 mg BID (Day 1-21) → 20 mg OD thereafter 4. Endpoint Definitions Primary Efficacy Endpoint Absolute reduction in RV/LV ratio from baseline to 48 hours post-intervention, measured by blinded core-lab CTPA analysis. Primary Safety Endpoint Composite Major Adverse Events (MAEs) within 48 hours, including: Procedure-related mortality Major bleeding per VARC-2 criteria: Fatal bleeding Intracranial hemorrhage Bleeding causing ≥3 g/dL hemoglobin drop or transfusion of ≥2 units Bleeding requiring surgical intervention Treatment-related clinical deterioration: Unplanned mechanical ventilation Sustained hypotension (SBP \<90 mmHg for \>1 hour requiring vasopressors) Cardiopulmonary resuscitation New requirement for ECMO or emergency surgical embolectomy 5. Statistical Analysis Plan Sample Size: 142 subjects/group (total N=284) providing 90% power (α=0.05) to detect: Efficacy: Mean RV/LR reduction difference of 0.15 (SD=0.3) Safety: 40% relative risk reduction in MAEs (Group A: 10% vs. Group B: 17%) Analysis Sets: Primary analysis: Modified intention-to-treat (mITT; all randomized receiving ≥1 treatment component) Safety analysis: As-treated population Methods: Continuous variables: Mixed-effects repeated measures ANOVA Categorical variables: Cochran-Mantel-Haenszel test with stratification adjustment Time-to-event: Kaplan-Meier with log-rank test 6. Quality Assurance Endpoint Adjudication Committee: Blinded to treatment allocation Data Monitoring: Independent DSMB reviewing unblinded safety data quarterly Procedure Standardization: All interventionalists certified via simulation training (≥5 proctored cases) Centralized core lab for CTPA RV/LV measurements Ethical Compliance: Approved by institutional review boards at all sites (NCT# pending). Trial conducted per Declaration of Helsinki. Key Advantages of Expanded Protocol Stratified randomization controls confounding from baseline RV strain heterogeneity. VARC-2 bleeding criteria enhance comparability with cardiovascular intervention trials. Core-lab blinded CTPA analysis eliminates measurement bias in efficacy assessment. Pre-specified safety triggers (e.g., Hb drop thresholds) enable objective MAE classification. Standardized anticoagulation bridging minimizes post-procedural thrombotic risk variability.