Catheter-Directed Pulmonary Reperfusion in Treatment of Pulmonary Embolism Patients

Catheter-Directed Pulmonary Re Perfusion in Treatment of Intermediate and High Risk Pulmonary Embolism Patients and Its Impact on Pulmonary Artery Pressure

• Primary objective: to evaluate the success and mortality rates of catheter-directed reperfusion therapy in comparison to traditional use of systemic intravenous fibrinolytic therapy, will focus at safety of such management measured by in-hospital mortality and prevalence of severe adverse events.
• Secondary objective: to assess the feasibility of catheter-directed reperfusion in management of intermediate and high risk pulmonary embolism in Assiut University hospital and its reflection on pulmonary artery pressure

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Embolism
• Intervention / Treatment: Procedure: mechanical fragmentation; Procedure: In Situ thrombolysis

Detailed Description

Venous thromboembolic disease represents one of the most important causes of cardiovascular death in the world. Symptomatic pulmonary embolism (PE) occurs in about 500,000 patients annually, with an estimated mortality as high as 30% in high-risk patients .

High-risk pulmonary embolism clinically manifests with hemodynamic instability and systemic hypotension (systolic blood pressure < 90 mm Hg, pressure drop of more than 40 mm Hg or requiring administration of inotropic agents. In this form of PE (pulmonary embolism) imaging studies usually reveal a "saddle embolus" at the bifurcation of the pulmonary trunk, embolism of the main pulmonary artery, or embolic occlusion of at least two lobar arteries.

Mortality in high-risk pulmonary embolism is at the level of 60%, and in 66% of these patients fatal outcomes take place during the first hours from the onset of clinical symptoms. The remaining patients with severe pulmonary embolism , those with intermediate risk of mortality, do not reveal hypotension, but present with clinical symptoms comprising dyspnea and/or tachycardia. Estimated 30-day mortality in patients with intermediate risk PE (pulmonary embolism) is at the level of 15-20%, and these patients are at a risk of developing pulmonary hypertension and right ventricle heart failure. Given the fact that 40% of patients with class 4 or 5 of the Pulmonary Embolism Severity Index present with contraindications for systemic fibrinolytic therapy, Catheter-directed reperfusion therapy seems to be a promising alternative treatment modality.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aliaa Ahmed, MD; Phone Number: 201009087704; Email: aliaasalama49@gmail.com
• Study Contact Backup: Name: Arafa abo el Hassan, lecturer; Phone Number: 201017445151; Email: arafaelkady@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >18 years old.
• Both gender males and females.
• Patients with angiographically confirmed acute high risk pulmonary embolism with shock index >1.
• pulmonary arterial occlusion with >50% involvement of the central (main and/or lobar) pulmonary, and dysfunction of the right ventricle and elevated troponin.
• patients with high risk pulmonary embolism who remain unstable after receiving fibrinolysis
• patients with high risk PE pulmonary embolism who cannot receive fibrinolysis
• patients with intermediate high risk PE pulmonary embolism with adverse prognosis (new hemodynamic instability, worsening respiratory failure, severe RV (right ventricle) dysfunction, or major myocardial necrosis)

Exclusion Criteria:

• patients with echocardiographically confirmed right sided thrombi.
• patients with low-risk PE pulmonary embolism or submassive acute PE pulmonary embolism with minor RV (right ventricle) dysfunction, minor myocardial necrosis, and no clinical worsening
• Anaphylactic reaction to contrast media.
• Acute renal failure or severe chronic non-dialysis dependent kidney disease.
• Uncooperative patient

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: systemic thrombolysis group; patients without any contraindications for systemic fibrinolytic therapy will be treated with traditional systemic thrombolysis (intravenous administration of streptokinase).
Active Comparator: mechanical fragmentation group; patients will be treated with catheter-directed mechanical fragmentation under fluoroscopy guidance. This group will include patients with absolute contraindication for fibrinolytic therapy.	Procedure: mechanical fragmentation; patients who will be treated with catheter-directed mechanical fragmentation under fluoroscopy guidance. This group will include patients with absolute contraindication for fibrinolytic therapy
Active Comparator: In Situ thrombolysis group; patients will be treated with bed side administration of low dose of local thrombolytic therapy (In Situ) via a trans-Jugular Swan-Ganz pulmonary artery catheter. with guidance of the pressure waveforms obtained from SGC(Swan-Ganz pulmonary artery catheter) and echocardiography guidance for ideal Catheter placement. This group will include the patients with relative contraindications for systemic thrombolysis, contraindications for contrasted administration (patients with renal impairment) and also patients with contraindications for radiation exposure (pregnant women).	Procedure: In Situ thrombolysis; Group (C) will include the patients who will be treated with bed side administration of low dose of local thrombolytic therapy (In Situ) via a trans-Jugular Swan-Ganz pulmonary artery catheter. with guidance of the pressure waveforms obtained from SGC (Swan-Ganz catheter) and echocardiography guidance for ideal Catheter placement. This group will include the patients with relative contraindications for systemic thrombolysis, contraindications for contrasted administration (patients with renal impairment) and also patients with contraindications for radiation exposure (pregnant women).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of mortality (mortality rate)	number of deaths from total number of patients in each arm	30-day
Rate of complications	as major and minor bleedings	7 days
Rate of Success	number of cases with clinical success which defined as stabilization of hemodynamic parameters, resolution of hypoxia, survival from PE(pulmonary embolism) and restoring of right ventricular function (improvement of ghit ventricle and pulmonary artery pressure and decrease troponin level)	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Changes in mean blood pressure	the percent of change in mean arterial blood pressure	Baseline (measured at first admission) and compared with measurements the following second, eighth, and 24th hours of the intervention.
Mean pulmonary artery pressure	Mean pulmonary artery pressure will be estimated by transthoracic echocardiography	Baseline (at addmission) and 24 hours after catheter-directed intervention
Duration of ICU(intensive care unit) stay	the duration of ICU (intensive care unit) stay by days	"through study completion, an average of 1 year".
Duration of hospital stay	the duration of hospital stay by days	"through study completion, an average of 1 year".

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: mohamed M abd el hadi, prof, Professor of Chest Diseases and Tuberculosis; Study Director: Ayman k hassan, lecturer, Assiut University; Study Chair: olfat M El shinnawy, prof, Assiut University; Principal Investigator: Aliaa S Ahmed, MD, 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.
• Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, Greer IA, Heit JA, Hutchinson JL, Kakkar AK, Mottier D, Oger E, Samama MM, Spannagl M; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007 Oct;98(4):756-64.
• Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999 Apr 24;353(9162):1386-9. doi: 10.1016/s0140-6736(98)07534-5.
• Nassiri N, Jain A, McPhee D, Mina B, Rosen RJ, Giangola G, Carroccio A, Green RM. Massive and submassive pulmonary embolism: experience with an algorithm for catheter-directed mechanical thrombectomy. Ann Vasc Surg. 2012 Jan;26(1):18-24. doi: 10.1016/j.avsg.2011.05.026. Epub 2011 Aug 31.
• Anderson FA Jr, Zayaruzny M, Heit JA, Fidan D, Cohen AT. Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol. 2007 Sep;82(9):777-82. doi: 10.1002/ajh.20983.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 30, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 30, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 14, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: 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: CDR in PE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No