Fibrinolytic Deficit in Patients With Acute PE

Acute Pulmonary Embolism Clinical Trial

Official title:

Fibrinolytic Deficit in Patients With Acute Pulmonary Embolism

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04480892
• Other study ID #: 212490
• Status: Not yet recruiting
• Start date: August 2020
• Est. completion date: December 2024

Study information

• Verified date: July 2020
• Source: Loyola University
• Contact: Amir Darki, MD
• Phone: 708-216-4466
• Email: adarki[@]lumc.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Pulmonary Embolism
• Embolism
• Fibrinolytic Deficit
• Pulmonary Embolism

Locations

Country	Name	City	State
United States	Loyola University Medical Center	Maywood	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Loyola University	Boston Scientific Corporation

Country where clinical trial is conducted

United States, 

References & Publications (9)

Brailovsky, Y. et al. NOVEL BIOMARKERS FOR RISK STRATIFICATION IN ACUTE PULMONARY EMBOLISM. J. Am. Coll. Cardiol. 73, 2088 (2019

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. — View Citation

Kucher N, Boekstegers P, Müller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Müller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Härtel D, Grünwald 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. — View Citation

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, Galiè 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. — View Citation

Part 6: Hemostasis and Thrombosis, Chapter 35: Normal Hemostasis, Fibrinolysis, p. 642-645. Rodak's Hematology. (Saunders, 2020)

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):1382-92. doi: 10.1016/j.jcin.2015.04.020. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasminogen Activator Inhibitor-1 (PAI-1)	Laboratory analysis of blood sample for PAI-1 level	Baseline-Day 1
Primary	Alpha-2 Antiplasmin level (A2P)	Laboratory analysis of blood sample for A2P level	Baseline-Day 1
Primary	Thrombin Activatable Fibrinolysis Inhibitor (TAFI)	Laboratory analysis of blood sample for TAFI level	Baseline-Day 1
Primary	Tissue plasminogen activator (tPA)	Laboratory analysis of blood sample for tPA level	Baseline-Day 1
Primary	D-dimer	Laboratory analysis of blood sample for D-dimer level	Baseline-Day 1
Primary	Plasminogen	Laboratory analysis of blood sample for Plasminogen level	Baseline-Day 1
Primary	Fibrinogen	Laboratory analysis of blood sample for Fibrinogen level	Baseline-Day 1
Primary	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
Primary	Right Ventricular Function	Assessed by echocardiography	Baseline-Day 1
Primary	Pulmonary Artery Pressure	Pulmonary Artery Pressure (mmHg) will be measured for patients escalated to endovascular therapies in the cardiac cath laboratory	Baseline-Day 1
Primary	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