Mechanical Thrombectomy for Acute Pulmonary Embolism

• 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.
• 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

• 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

• 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

• 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

• 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.

Inclusion criteria

• 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.

Exclusion criteria

• Target vessel diameter <6 mm
• Calcification, plaque, or stenosis in target lesion
• Sustained systolic blood pressure <90 mmHg for >15 minutes or requiring vasopressors to maintain SBP ≥90 mmHg
• Peak pulmonary artery pressure >70 mmHg
• Hematocrit <28%
• History of chronic pulmonary hypertension
• Pre-existing left bundle branch block
• Chronic left heart failure with left ventricular ejection fraction (LVEF) ≤30%
• Renal dysfunction (serum creatinine >1.8 mg/dL or >159 μmol/L)
• Known coagulopathy or bleeding diathesis:

Platelet count <50×10⁹/L, or International Normalized Ratio (INR) >3

• Contraindications to antiplatelet/anticoagulant therapy
• Cardiothoracic or pulmonary surgery within 7 days prior
• Intracardiac thrombus
• Patients on extracorporeal membrane oxygenation (ECMO)
• Known hypersensitivity to iodinated contrast media
• Significant comorbidities complicating treatment/evaluation:

Active malignancy Acute infectious disease/sepsis Systemic conditions precluding procedure tolerance Life expectancy <1 year

• Pregnant or lactating women
• Concurrent participation in other drug/device trials
• Other investigator-determined unsuitability