Fibrinolytic Deficit in Patients With Acute PE

• ClinicalTrials.gov Identifier: NCT04480892
• Recruitment Status: Not yet recruiting
• First Posted: July 22, 2020
• Last Update Posted: July 22, 2020
• Sponsor: Loyola University
• Collaborator: Boston Scientific Corporation
• Information provided by (Responsible Party): Amir Darki, Loyola University

Tracking Information

• First Submitted Date: June 28, 2020
• First Posted Date: July 22, 2020
• Last Update Posted Date: July 22, 2020
• Estimated Study Start Date: August 2020
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 16, 2020)

• Plasminogen Activator Inhibitor-1 (PAI-1) [ Time Frame: Baseline-Day 1 ]
  Laboratory analysis of blood sample for PAI-1 level
• Alpha-2 Antiplasmin level (A2P) [ Time Frame: Baseline-Day 1 ]
  Laboratory analysis of blood sample for A2P level
• Thrombin Activatable Fibrinolysis Inhibitor (TAFI) [ Time Frame: Baseline-Day 1 ]
  Laboratory analysis of blood sample for TAFI level
• Tissue plasminogen activator (tPA) [ Time Frame: Baseline-Day 1 ]
  Laboratory analysis of blood sample for tPA level
• D-dimer [ Time Frame: Baseline-Day 1 ]
  Laboratory analysis of blood sample for D-dimer level
• Plasminogen [ Time Frame: Baseline-Day 1 ]
  Laboratory analysis of blood sample for Plasminogen level
• Fibrinogen [ Time Frame: Baseline-Day 1 ]
  Laboratory analysis of blood sample for Fibrinogen level
• Clinical Presentation Risk Score [ Time Frame: Baseline-Day 1 ]
  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.
• Right Ventricular Function [ Time Frame: Baseline-Day 1 ]
  Assessed by echocardiography
• Pulmonary Artery Pressure [ Time Frame: Baseline-Day 1 ]
  Pulmonary Artery Pressure (mmHg) will be measured for patients escalated to endovascular therapies in the cardiac cath laboratory
• Cardiac Output [ Time Frame: Baseline-Day 1 ]
  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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Fibrinolytic Deficit in Patients With Acute PE
• Official Title: Fibrinolytic Deficit in Patients With Acute Pulmonary Embolism
• Brief 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.
• 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 [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: 1 Day

Biospecimen

Retention:   Samples With DNA

Description:

Blood samples drawn for clinical evaluation of PE will be collected after analysis complete, de-identified, re-centrifuged, aliquoted, and stored in -80 freezer. Once all 100 patient samples have been collected, samples will be analyzed for fibrinolytic biomarkers.

• Sampling Method: Non-Probability Sample
• Study Population: Patients with acute PE being treated by the PERT.

Condition

• Acute Pulmonary Embolism
• Fibrinolytic Deficit

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

Publications *

• 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.
• 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.
• 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.
• 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.
• 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)

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: July 16, 2020): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amir Darki, MD; 708-216-4466; adarki@lumc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04480892
• Other Study ID Numbers: 212490
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Amir Darki, Loyola University
• Original Responsible Party: Same as current
• Current Study Sponsor: Loyola University
• Original Study Sponsor: Same as current
• Collaborators: Boston Scientific Corporation

Investigators

• Principal Investigator: Amir Darki, MD; Loyola University

• PRS Account: Loyola University
• Verification Date: July 2020