Fibrinolytic Deficit in Patients With Acute PE

Fibrinolytic Deficit in Patients With Acute Pulmonary Embolism

Fibrinolysis is the body's process that prevents blood clots. The investigators hypothesize that patients presenting with acute pulmonary embolism (PE) or blood clots in the lungs differ in their fibrinolytic deficit phenotype. The investigators aim to use biomarkers directly involved in endogenous fibrinolytic cascade including PAI-1, Alpha-2-Antiplasmin (A2A), TAFI, D-dimer, and Fibrinogen to phenotypically characterize patients presenting with acute PE and to correlate these biomarkers with clinical, echocardiographic, computed tomography (CT), and functional status outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Pulmonary Embolism; Fibrinolytic Deficit

Detailed Description

Patients (n=100) identified by the Pulmonary Embolism Response Team (PERT) suffering from a PE will be identified by the PI. Blood plasma samples from these patients which have been drawn for routine lab tests will be identified and the Sub-I who will pick the samples up from the clinical lab after the routine analysis has been completed. These samples will be de-identified by giving them a study number. These samples will be recentrifuged and aliquoted. Samples will be stored in a -80ᵒC freezer in the Hemostasis & Thrombosis Research Laboratory. When all 100 de-identified samples have been collected they will be analyzed blindly by the technical staff of the hemostasis laboratory for the fibrinolytic parameters PAI-1, Alpha-2-Antiplasmin, TAFI, tPA, D-dimer, Plasminogen, and Fibrinogen. PAI-1 and TAFI will be quantified with an Enzyme Linked-Immuno-Sorbent Assay (ELISA), while A2A is measured using functional assay. PAI-1 is measured as ug/ml, while TAFI and A2A are measured as % of normal controls. Normal controls are derived from pooled normal human plasma from volunteers purchased from outside vendor. Results will be compiled and sent to the PERT team for analysis and correlation withclinical, echocardiographic, computed tomography (CT), and functional status outcomes.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Amir Darki, MD; Phone Number: 708-216-4466; Email: adarki@lumc.edu

Study Locations

• United States
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
      • Contact: Amir Darki, MD; Phone Number: 708-216-4466; Email: adarki@lumc.edu
      • Sub-Investigator: Debra Hoppensteadt-Moorman, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute PE being treated by the PERT.

Description

Inclusion Criteria:

• Patients age 18 - 90 years
• Patients suffering an acute PE
• Blood collected for clinical evaluation of PE

Exclusion Criteria:

• Blood not collected or not sufficient quantity/quality

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasminogen Activator Inhibitor-1 (PAI-1)	Laboratory analysis of blood sample for PAI-1 level	Baseline-Day 1
Alpha-2 Antiplasmin level (A2P)	Laboratory analysis of blood sample for A2P level	Baseline-Day 1
Thrombin Activatable Fibrinolysis Inhibitor (TAFI)	Laboratory analysis of blood sample for TAFI level	Baseline-Day 1
Tissue plasminogen activator (tPA)	Laboratory analysis of blood sample for tPA level	Baseline-Day 1
D-dimer	Laboratory analysis of blood sample for D-dimer level	Baseline-Day 1
Plasminogen	Laboratory analysis of blood sample for Plasminogen level	Baseline-Day 1
Fibrinogen	Laboratory analysis of blood sample for Fibrinogen level	Baseline-Day 1
Clinical Presentation Risk Score	Based on vital signs (heart rate, blood pressure, oxygen requirements, and labs (CBC, lactate, troponin, and BNP, clinical presentation will be characterized as low, intermediate, or high risk.	Baseline-Day 1
Right Ventricular Function	Assessed by echocardiography	Baseline-Day 1
Pulmonary Artery Pressure	Pulmonary Artery Pressure (mmHg) will be measured for patients escalated to endovascular therapies in the cardiac cath laboratory	Baseline-Day 1
Cardiac Output	Cardiac Output, the volume of blood pumped from the ventricle per heartbeat (mL/min), will be measured for patients escalated to endovascular therapies in the cardiac cath laboratory.	Baseline-Day 1

Collaborators and Investigators

• Sponsor: Loyola University
• Collaborators: Boston Scientific Corporation
• Investigators: Principal Investigator: Amir Darki, MD, Loyola University

Publications and helpful links

General Publications

• Chatterjee S, Chakraborty A, Weinberg I, Kadakia M, Wilensky RL, Sardar P, Kumbhani DJ, Mukherjee D, Jaff MR, Giri J. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21. doi: 10.1001/jama.2014.5990.
• Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; "MOPETT" Investigators. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013 Jan 15;111(2):273-7. doi: 10.1016/j.amjcard.2012.09.027. Epub 2012 Oct 24.
• Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.
• Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Hartel D, Grunwald H, Empen K, Baumgartner I. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28;129(4):479-86. doi: 10.1161/CIRCULATIONAHA.113.005544. Epub 2013 Nov 13.
• Piazza G, Hohlfelder B, Jaff MR, Ouriel K, Engelhardt TC, Sterling KM, Jones NJ, Gurley JC, Bhatheja R, Kennedy RJ, Goswami N, Natarajan K, Rundback J, Sadiq IR, Liu SK, Bhalla N, Raja ML, Weinstock BS, Cynamon J, Elmasri FF, Garcia MJ, Kumar M, Ayerdi J, Soukas P, Kuo W, Liu PY, Goldhaber SZ; SEATTLE II Investigators. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1382-1392. doi: 10.1016/j.jcin.2015.04.020.
• Tapson VF, Sterling K, Jones N, Elder M, Tripathy U, Brower J, Maholic RL, Ross CB, Natarajan K, Fong P, Greenspon L, Tamaddon H, Piracha AR, Engelhardt T, Katopodis J, Marques V, Sharp ASP, Piazza G, Goldhaber SZ. A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial. JACC Cardiovasc Interv. 2018 Jul 23;11(14):1401-1410. doi: 10.1016/j.jcin.2018.04.008.
• Zhang Z, Zhai ZG, Liang LR, Liu FF, Yang YH, Wang C. Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: a systematic review and meta-analysis. Thromb Res. 2014 Mar;133(3):357-63. doi: 10.1016/j.thromres.2013.12.026. Epub 2013 Dec 23.
• Brailovsky, Y. et al. NOVEL BIOMARKERS FOR RISK STRATIFICATION IN ACUTE PULMONARY EMBOLISM. J. Am. Coll. Cardiol. 73, 2088 (2019
• Part 6: Hemostasis and Thrombosis, Chapter 35: Normal Hemostasis, Fibrinolysis, p. 642-645. Rodak's Hematology. (Saunders, 2020)

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: June 28, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 16, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Acute Pulmonary Embolism; Fibrinolysis; Fibrinolytic System
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: 212490

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: No