Pulmonary Embolism, Venous Thromboembolism
Conditions
Keywords
Acute Pulmonary Embolism, Intermediate-High Risk, Anticoagulation, Thrombolysis
Brief summary
This study aims to compare the effectiveness and safety of three treatment strategies (Anticoagulation, Thrombolysis, and Mechanical Thrombectomy) for patients with intermediate-high risk acute pulmonary embolism (PE) in a real-world setting. Approximately 1,300 patients will be enrolled across multiple centers in China. Patients will be followed for 90 days to assess mortality, heart function recovery, bleeding risks, and quality of life. The results will help guide personalized treatment decisions and healthcare policy.
Detailed description
Background: Acute pulmonary embolism (PE) is a severe manifestation of venous thromboembolism (VTE). Intermediate-high risk PE accounts for 20-30% of all PE cases with significant mortality driven by right ventricular (RV) dysfunction. Current guidelines recommend anticoagulation for all, with thrombolysis or mechanical thrombectomy as rescue or alternative therapies. However, there is significant heterogeneity in real-world treatment selection and a lack of head-to-head comparative evidence among the three strategies in complex real-world populations. Objective: To compare the 30-day and 90-day all-cause mortality and 48-hour RV/LV ratio improvement rate among three treatment strategies (Anticoagulation, Thrombolysis, Mechanical Thrombectomy) in patients with intermediate-high risk acute PE. Design: This is a prospective, multicenter, non-randomized, pragmatic cohort study. Treatment allocation is based on routine clinical decision-making (natural allocation) without investigator intervention. Advanced statistical methods (Propensity Score Matching/Weighting, Instrumental Variable analysis) will be used to control for confounding factors. Participants: 1,300 patients with confirmed acute intermediate-high risk PE (RV/LV ratio ≥0.9 and elevated cardiac biomarkers, hemodynamically stable). There are no age limits to reflect real-world diversity. Interventions/Exposures: 1. Anticoagulation (AC): Standard anticoagulant therapy (LMWH, DOAC, UFH, or Warfarin). 2. Thrombolysis (TL): Systemic thrombolysis or Catheter-Directed Thrombolysis (CDT) using agents like Urokinase, Alteplase, etc. 3. Mechanical Thrombectomy (MT): Mechanical removal of thrombus using FDA/NMPA approved devices (e.g., Indigo, FlowTriever, Acoscream), with or without adjunctive anticoagulation/thrombolysis. Outcomes: * Primary: 30-day and 90-day all-cause mortality; 48-hour RV/LV ratio improvement rate (≥15% reduction). * Secondary: Clinical deterioration, major bleeding (ISTH/GUSTO/BARC), functional status (6MWT, NYHA, PVFS), quality of life (PEmb-QoL, EQ-5D-5L), PE recurrence, and healthcare resource utilization. Follow-up: Patients will be followed at 48 hours, 7 days, 30 days, and 90 days.
Interventions
DRUGAnticoagulants
Low Molecular Weight Heparin (LMWH), Direct Oral Anticoagulants (DOAC), Unfractionated Heparin (UFH), or Warfarin according to guideline-standard regimens.
DRUGThrombolytic Agents
Urokinase, Pro-urokinase, Alteplase, or Tenecteplase administered systemically or via catheter.
DEVICEMechanical Thrombectomy Devices
Any FDA/NMPA approved mechanical thrombectomy device (e.g., Indigo, FlowTriever, Acoscream) used for clot removal.
Sponsors
Nanjing First Hospital, Nanjing Medical University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Age unlimited (reflecting real-world population). * Symptom duration of acute PE ≤ 14 days. * Confirmed acute PE by CTPA involving main or lobar pulmonary arteries. * Defined as Intermediate-High Risk PE meeting all of the following: * RV/LV ratio ≥ 0.9 (by CT or Echocardiography). * Elevated cardiac biomarkers (Troponin \> 99th percentile or BNP \> 100 pg/mL). * Hemodynamically stable (SBP ≥ 90 mmHg, no vasopressors required). * Able to provide informed consent and complete follow-up.
Exclusion criteria
* Already received thrombolysis or mechanical thrombectomy for the current episode prior to enrollment. * Unable to obtain baseline or follow-up CTPA imaging. * (Note: Unlike strict RCTs, patients with cancer, renal insufficiency, or advanced age are NOT excluded to ensure real-world representativeness).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality at 30 Days | 30 days | The percentage of participants who die from any cause within 30 days of enrollment. |
| All-Cause Mortality at 90 Days | 90 days | The percentage of participants who die from any cause within 90 days of enrollment. |
| Right Ventricular to Left Ventricular (RV/LV) Ratio Improvement Rate at 48 Hours | 48 hours ± 6 hours | The proportion of participants with a reduction in RV/LV ratio ≥15% from baseline measured by CTPA or Echocardiography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Bleeding Events | 48 hours, 7 days, 30 days, 90 days | Incidence of major bleeding defined by ISTH, GUSTO, or BARC criteria (including intracranial hemorrhage). |
| Clinical Deterioration | 48 hours, 7 days | Composite of hemodynamic instability, need for rescue therapy (escalation to thrombolysis/MT/ECMO), intubation, or PE-related death. |
| 6-Minute Walk Test (6MWT) Distance | 30 days, 90 days | Change in walking distance from baseline (estimated) to follow-up. Minimal Clinically Important Difference (MCID) ≥30 meters. |
| Post-VTE Functional Status (PVFS) Score | 30 days, 90 days | Assessment of functional limitation due to VTE (Scale 0-5). |
| Quality of Life (PEmb-QoL) | 90 days | The questionnaire consists of 9 questions containing 40 items, which are organized into 6 domains: Frequency of Complaints (FC): Assesses the frequency of respiratory and general symptoms (e.g., dyspnea, chest pain). Daily Activity Limitations (AL): Measures limitations in performing activities of daily living (ADL). Work-related Problems (WP): Evaluates difficulties in performing work or school duties. Social Limitations (SL): Assesses restrictions on social activities. Intensity of Complaints (IC): Measures the severity of pain and breathlessness. Emotional Complaints (EC): Captures anxiety, frustration, and fear related to the disease. |
| Symptomatic PE Recurrence | 90 days | Confirmed recurrent PE via CTPA or V/Q scan. |
| ICU Length of Stay | From ICU admission to ICU discharge, assessed up to 30 days | Duration of intensive care unit stay during the index hospitalization |
| Total Hospital Length of Stay | From hospital admission to hospital discharge, assessed up to 90 days | Duration of index hospitalization from emergency department admission to hospital discharge |
| Total Medical Costs | Through 90 days | Direct medical costs incurred during index hospitalization and within 90 days of enrollment, including medications, procedures, and hospitalization |
Countries
China
Contacts
CONTACThe xu Dr, doctor
Outcome results
None listed