Catheter Directed Therapy in Intermediate Risk Pulmonary Embolism Patients

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

Aim of the work:

1. To compare conventional medical therapy versus catheter-directed therapy in intermediate high risk acute pulmonary embolism.
2. To define predictors of progression from intermediate to high-risk in medically-treated patients for ideal timing for intervention.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Embolism Subacute Massive
• Intervention / Treatment: Procedure: Mechanical embolectomy: by hydromechanical defragmentation by pigtail; Device: Suction embolectomy by the Penumbra Indigo aspiration system

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Routine labs are withdrawn, including cardiac troponin.Methods: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:

1. Echocardiography findings that are indicative of RV dysfunction

   • tricuspid annular plane systolic excursion (TAPSE)
   • S' Velocity
   • the McConnell's sign
2. RV dilation
3. interventricular septal flattening.
4. elevated right ventricular pressures
5. plethoric inferior vena cava
6. tricuspid regurgitation
7. Direct visualization of thromboembolic in the RT heart and PA
8. RV stroke volume measured by RVOT VTI.
9. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Shrouk K Ali, MSc; Phone Number: +0201225134030; Email: shrouk31@aun.edu.eg
• Study Contact Backup: Name: Ayman Kh Hassan, MD; Phone Number: +0201094438055; Email: Aymankhairy11@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: catheter directed therapy group in intermediate risk pulmonary embolism patients; 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; 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; Device: Suction embolectomy by the Penumbra Indigo aspiration system; 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
Active Comparator: medical therapy group in intermediate risk pulmonary embolism patients; in this arm, intermediated risk pulmonary embolism patients is treated by routine anticoagulation only.	Procedure: Mechanical embolectomy: by hydromechanical defragmentation by pigtail; 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; Device: Suction embolectomy by the Penumbra Indigo aspiration system; 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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implementation of pulmonary embolism response team at Assiut university hospitals	institutional reconstruction and communication between different departments (chest, cardiology, radiology and clinical pathology departments) aiming to implement a pulmonary embolism response team with clear structure and operational levels for decision making	up to 2 years

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Shrouk K Ali, MSc, Assiut University

Publications and helpful links

General Publications

• Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galie N, Gibbs JS, Huisman MV, Humbert M, Kucher N, Lang I, Lankeit M, Lekakis J, Maack C, Mayer E, Meneveau N, Perrier A, Pruszczyk P, Rasmussen LH, Schindler TH, Svitil P, Vonk Noordegraaf A, Zamorano JL, Zompatori M; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014 Nov 14;35(43):3033-69, 3069a-3069k. doi: 10.1093/eurheartj/ehu283. Epub 2014 Aug 29. No abstract available. Erratum In: Eur Heart J. 2015 Oct 14;36(39):2666. Eur Heart J. 2015 Oct 14;36(39):2642.
• Kroupa J, Buk M, Weichet J, Malikova H, Bartova L, Linkova H, Ionita O, Kozel M, Motovska Z, Kocka V. A pilot randomised trial of catheter-directed thrombolysis or standard anticoagulation for patients with intermediate-high risk acute pulmonary embolism. EuroIntervention. 2022 Oct 7;18(8):e639-e646. doi: 10.4244/EIJ-D-21-01080.
• Giri J, Sista AK, Weinberg I, Kearon C, Kumbhani DJ, Desai ND, Piazza G, Gladwin MT, Chatterjee S, Kobayashi T, Kabrhel C, Barnes GD. Interventional Therapies for Acute Pulmonary Embolism: Current Status and Principles for the Development of Novel Evidence: A Scientific Statement From the American Heart Association. Circulation. 2019 Nov 12;140(20):e774-e801. doi: 10.1161/CIR.0000000000000707. Epub 2019 Oct 4. Review.
• Hassan AKM, Ahmed H, Ahmed Y, Elfadl AA, Omar A. Efficacy and safety of hydro-mechanical defragmentation in intermediate- and high-risk pulmonary embolism. Egypt Heart J. 2021 Sep 25;73(1):84. doi: 10.1186/s43044-021-00204-2.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 30, 2022
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: October 16, 2022
• First Submitted That Met QC Criteria: November 9, 2022
• First Posted (Actual): November 10, 2022

Study Record Updates

• Last Update Posted (Actual): November 10, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: catheter directed therapy; intermediate risk pulmonary embolism
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: CDT in pulmonary embolism

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes