Catheter Directed Therapy in Intermediate Risk Pulmonary Embolism Patients

Study Overview
=================
Brief Summary
-----------------
Aim of the work: To compare conventional medical therapy versus catheter-directed therapy in intermediate high risk acute pulmonary embolism. To define predictors of progression from intermediate to high-risk in medically-treated patients for ideal timing for intervention.

Detailed Description
-----------------
Based on history, physical examination, surface 12-lead ECG, bed-side echocardiography, patients with a high probability of acute pulmonary embolism are selected and subjected to CT pulmonary angiography to confirm the diagnosis and calculate the pulmonary artery obstruction score. Routine labs are withdrawn, including cardiac troponin.Methods: Detailed TTE will be done with emphasis on the following indicators of RV strain and/or dysfunction: Echocardiography findings that are indicative of RV dysfunction tricuspid annular plane systolic excursion (TAPSE) S' Velocity the McConnell's sign RV dilation interventricular septal flattening. elevated right ventricular pressures plethoric inferior vena cava tricuspid regurgitation Direct visualization of thromboembolic in the RT heart and PA RV stroke volume measured by RVOT VTI. LV stroke volume measured by LVOT VTI Intermediate-high risk patient will be identified (based on the calculated pulmonary embolism severity index, RV dysfunction on TTE and/or CT, cardiac troponin), and then randomized to either receiving conventional medical treatment or catheter-directed interventional therapy if the patient consents. 7. Catheter directed therapy A. Mechanical embolectomy: Mechanical fragmentation will be done using a 6 F pigtail catheter inserted inside the thrombus guided by the CTPA images. Hydro-mechanical defragmentation (HMD) is one of the CDT modalities for high-risk PE patients, in which rapid pigtail rotation is combined with heparinized saline injection for thrombus fragmentation.(4) B. Suction embolectomy: Suction embolectomy was one of the earliest techniques for transcatheter treatment of PE, and was introduced by Greenfield et al, using a 12-Fr catheter with a cup on its distal end. Suction was applied manually to the catheter hub with a large syringe. (13) The Penumbra Indigo aspiration system (Penumbra Inc., Alameda, CA, USA) that will be used, is an 8-Fr device and its associated tubing, pump, and separator, has the flexibility for placement in segmental branches of the pulmonary arteries. The Indigo aspiration system is indicated for use in the peripheral arterial system and the pulmonary arteries, receiving U.S. Food and Drug Administration 510(k) clearance for PE in December 2019.(14) C. Catheter directed thrombolysis: Catheter-directed thrombolysis allows delivery of the thrombolytic agent directly to the area of highest embolic burden via a catheter. Intermediate-high risk patient will be identified (based on the calculated pulmonary embolism severity index, RV dysfunction on TTE and/or CT, cardiac troponin), and then randomized to either receiving conventional medical treatment or catheter-directed interventional therapy if the patient consents.

Official Title
-----------------
Catheter Directed Therapy for Intermediate Risk Pulmonary Embolism Patients Guided by Prediction Model for Impending Shock

Conditions
-----------------
Pulmonary Embolism Subacute Massive

Intervention / Treatment
-----------------
* Procedure: Mechanical embolectomy: by hydromechanical defragmentation by pigtail
* Device: Suction embolectomy by the Penumbra Indigo aspiration system


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acute pulmonary embolism patients (confirmed by CT pulmonary angiography [CTPA]) symptoms started within 15 days of enrollment intermediate-high risk pulmonary embolism patients , i.e., who have all of the following risk indicators combined :(2) i.Pulmonary Embolism Severity Index (PESI) class III-V or sPESI ≥1, ii.AND RV dysfunction on TTE or CTPA, iii.AND elevated cardiac troponin levels with none of the following high-risk presentations: cardiac arrest, systolic blood pressure <90 mmHg, or vasopressors required to achieve a BP ≥90 mmHg despite an adequate filling status, or end-organ hypoperfusion. Exclusion Criteria: high risk patients who are hemodynamically unstable (cardiogenic shock, SBP <90 mmHg, or use of intotropic support). low risk patients with no RV dysfunction. Patients with history of CTEPH (or previous acute PE) Patients known to have other pulmonary hypertension, apart from group IV (CTEPH). Patients with sever kidney injury (eGFR <30 mg/dl/1.7m2).

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled, open-label, parallel-assignment, prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: catheter directed therapy group in intermediate risk pulmonary embolism patients<br>in this arm, intermediated risk pulmonary embolism patients is treated by intervention in the form of: A. Mechanical embolectomy: by hydromechanical defragmentation by pigta B. Suction embolectomy: using The Penumbra Indigo aspiration system C. Catheter directed thrombolysis: | Procedure: Mechanical embolectomy: by hydromechanical defragmentation by pigtail<br>* Hydro-mechanical defragmentation (HMD) is one of the CDT modalities for high-risk PE patients, in which rapid pigtail rotation is combined with heparinized saline injection for thrombus fragmentation<br>Device: Suction embolectomy by the Penumbra Indigo aspiration system<br>* The Penumbra Indigo aspiration system (Penumbra Inc., Alameda, CA, USA) that will be used, is an 8-Fr device and its associated tubing, pump, and separator, has the flexibility for placement in segmental branches of the pulmonary arteries. 510(k) Number :K160449 FOIA Releasable 510(k) K160449 Device Name:Penumbra System, Penumbra Pump MAX<br>|
| Active Comparator: medical therapy group in intermediate risk pulmonary embolism patients<br>in this arm, intermediated risk pulmonary embolism patients is treated by routine anticoagulation only. | Procedure: Mechanical embolectomy: by hydromechanical defragmentation by pigtail<br>* Hydro-mechanical defragmentation (HMD) is one of the CDT modalities for high-risk PE patients, in which rapid pigtail rotation is combined with heparinized saline injection for thrombus fragmentation<br>Device: Suction embolectomy by the Penumbra Indigo aspiration system<br>* The Penumbra Indigo aspiration system (Penumbra Inc., Alameda, CA, USA) that will be used, is an 8-Fr device and its associated tubing, pump, and separator, has the flexibility for placement in segmental branches of the pulmonary arteries. 510(k) Number :K160449 FOIA Releasable 510(k) K160449 Device Name:Penumbra System, Penumbra Pump MAX<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1.comparison between conventional medical therapy and catheter-directed therapy in intermediate high risk acute pulmonary embolism patients | comparison in intermediate high risk acute pulmonary embolism patients between conventional medical therapy and catheter-directed therapy as regarding safety and efficacy of the therapy by clinical assessment of occurrence of major adverse cardiac events. | up to 2 years | 
| 1.comparison between conventional medical therapy and catheter-directed therapy in intermediate high risk acute pulmonary embolism patients | comparison in intermediate high risk acute pulmonary embolism patients between conventional medical therapy and catheter-directed therapy as regarding safety and efficacy of the therapy by echocardiographic assessment of right ventricular function by TAPSE (mm) , RV/LV diameter ratio ,TR peak gradient (mmHg) | up to 2 years | 
| 1.comparison between conventional medical therapy and catheter-directed therapy in intermediate high risk acute pulmonary embolism patients | comparison in intermediate high risk acute pulmonary embolism patients between conventional medical therapy and catheter-directed therapy as regarding safety and efficacy of the therapy by CT pulmonary angiography to asses embolus size and Pulmonary artery obstruction index | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| predictors of progression from intermediate to high-risk acute pulmonary embolism patients | identifying predictors for ideal timing for intervention in intermediate risk pulmonary embolism patients who are medically-treated by new echocardiographic parameters (LVOT velocity time integral and RVOT velocity time integral) | up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
catheter directed therapy, intermediate risk pulmonary embolism