Dynamics of Platelet Activation in Patients With Ventricular Assist Device (VAD)

Thrombosis Clinical Trial

— PASVAD  

Official title:

Analysis of the Platelet Activity State in Patients Implanted With Ventricular Assist Device (VAD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03255928
• Other study ID #: PASVAD v. n°1 10/03/2017
• Status: Recruiting
• Start date: June 29, 2017
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Scientific Institute San Raffaele
• Contact: Filippo Consolo, PhD
• Phone: +390226436153
• Email: consolo.filippo[@]unisr.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Consenting patients with end-stage heart failure that are implanted with/candidates for implant of a short-term/durable mechanical circulatory support device (e.g.: percutaneous microaxial pumps (Impella), extracorporeal membrane oxygenator (ECMO), Ventricular Assist Device (VAD) will be enrolled in the study. Aim of the study is to evaluate the patients' haemostatic and coagulation profile, how it interacts with the support device as well as the effect of antithrombotic drugs. From these data, it will be possible to derive the mechanisms triggering post-implant thromboembolic/hemorrhagic complications and to identify potential therapeutic targets.

Description:

The study is aimed at evaluating the patients' haemostatic and coagulation profile focusing, in particular, on platelet function. Platelet function will be analyzed utilizing two innovative analytic diagnostic tests, namely i) the Platelet Activity State (PAS) assay and ii) the Thrombin Generation Test (TGT). PAS values and TGT will be measured at different time-points over the course of support: i) before the implant of the support system, to define baseline patients' characteristics; ii) in the early-post implant, during patient hospitalization; iii) during long-term follow up, to evaluate the dynamics of platelet function over the course of support and potential alterations of platelet-mediated haemostatic processes; iv) at the occurrence of any thromboembolic/hemorrhagic complication or following a modification of the antithrombotic pharmacological therapy. Platelet function will be evaluated through: i) the Platelet Activity State (PAS) assay, a biochemical assay able to quantify the platelet thrombin production rate and to correlate this rate with the actual level of platelet activation (i.e., the platelet pro-thrombotic tendency); ii) the Thrombin Generation Test (TGT), a biochemical assay that the investigators have properly modified to account selectively for the platelet contribution on plasmatic thrombin generation. PAS and TGT experimental values will be correlated with the occurrences of post-implant complications. Experimental values will be also correlated with standard clinical parameters of coagulation and hemolysis, such as: platelet count, hematocrit, hemoglobin, prothrombin time (PT), activated partial thromboplastin time (aPTT), International Normalized Ratio (INR), D-Dimer, Fibrinogen, L-lactate dehydrogenase, haptoglobin, plasma-free hemoglobin, and C-reactive protein levels. Also levels of thrombin-antithrombin complex, Von Willebrand factor, prothrombin1,2 fraction and tissue factor, will be measured and recorded. In addition, pump (i.e. VAD) working parameters (i.e., rotation velocity, cardiac outflow and power consumption) will be recorded. Log-files of the pump will be downloaded and analyzed to characterize the correlation with the development of adverse events (AV). Finally, antithrombotic therapy will be recorded and used in the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• All consenting patients candidates for short-term (Impella, ECMO) or durable (LVAD) mechanical circulatory support device implantation
• All consenting patients that are implanted with short-term (Impella, ECMO) or durable (LVAD) mechanical circulatory support device

Exclusion Criteria:

• Patients < 18-years old

Related Conditions & MeSH terms

• Blood Coagulation Disorder
• Blood Coagulation Disorders
• Failure;Ventricular
• Hemostatic Disorders
• Platelet Dysfunction Due to Aspirin
• Platelet Thrombus
• Thrombosis

Intervention

Diagnostic Test:
• PAS assay, TGT
Evaluation of platelet function

Locations

Country	Name	City	State
Italy	San Raffaele Scientifc Institute - Cardiothoracic Intensive Care Unit	Milano	MI

Sponsors (2)

Lead Sponsor	Collaborator
Scientific Institute San Raffaele	Università Vita-Salute San Raffaele

Country where clinical trial is conducted

Italy, 

References & Publications (12)

Consolo F, Pozzi L, Sferrazza G, Della Valle P, D'Angelo A, Slepian MJ, Pappalardo F. Which Antiplatelet Therapy in Patients With Left Ventricular Assist Device and Aspirin Allergy? Ann Thorac Surg. 2018 Feb;105(2):e47-e49. doi: 10.1016/j.athoracsur.2017.09.022. — View Citation

Consolo F, Sferrazza G, Motolone G, Contri R, Valerio L, Lembo R, Pozzi L, Della Valle P, De Bonis M, Zangrillo A, Fiore GB, Redaelli A, Slepian MJ, Pappalardo F. Platelet activation is a preoperative risk factor for the development of thromboembolic complications in patients with continuous-flow left ventricular assist device. Eur J Heart Fail. 2018 Apr;20(4):792-800. doi: 10.1002/ejhf.1113. Epub 2017 Dec 28. — View Citation

Consolo F, Sferrazza G, Motolone G, Pieri M, De Bonis M, Zangrillo A, Redaelli A, Slepian MJ, Pappalardo F. Shear-Mediated Platelet Activation Enhances Thrombotic Complications in Patients With LVADs and Is Reversed After Heart Transplantation. ASAIO J. 2019 May/Jun;65(4):e33-e35. doi: 10.1097/MAT.0000000000000842. — View Citation

Consolo F, Sheriff J, Gorla S, Magri N, Bluestein D, Pappalardo F, Slepian MJ, Fiore GB, Redaelli A. High Frequency Components of Hemodynamic Shear Stress Profiles are a Major Determinant of Shear-Mediated Platelet Activation in Therapeutic Blood Recirculating Devices. Sci Rep. 2017 Jul 10;7(1):4994. doi: 10.1038/s41598-017-05130-5. — View Citation

Jesty J, Bluestein D. Acetylated prothrombin as a substrate in the measurement of the procoagulant activity of platelets: elimination of the feedback activation of platelets by thrombin. Anal Biochem. 1999 Jul 15;272(1):64-70. doi: 10.1006/abio.1999.4148. — View Citation

Rogers JG, Pagani FD, Tatooles AJ, Bhat G, Slaughter MS, Birks EJ, Boyce SW, Najjar SS, Jeevanandam V, Anderson AS, Gregoric ID, Mallidi H, Leadley K, Aaronson KD, Frazier OH, Milano CA. Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure. N Engl J Med. 2017 Feb 2;376(5):451-460. doi: 10.1056/NEJMoa1602954. — View Citation

Sheriff J, Bluestein D, Girdhar G, Jesty J. High-shear stress sensitizes platelets to subsequent low-shear conditions. Ann Biomed Eng. 2010 Apr;38(4):1442-50. doi: 10.1007/s10439-010-9936-2. Epub 2010 Feb 5. — View Citation

Sheriff J, Girdhar G, Chiu WC, Jesty J, Slepian MJ, Bluestein D. Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device. J Thromb Thrombolysis. 2014 May;37(4):499-506. doi: 10.1007/s11239-013-0997-6. — View Citation

Slaughter MS, Pagani FD, McGee EC, Birks EJ, Cotts WG, Gregoric I, Howard Frazier O, Icenogle T, Najjar SS, Boyce SW, Acker MA, John R, Hathaway DR, Najarian KB, Aaronson KD; HeartWare Bridge to Transplant ADVANCE Trial Investigators. HeartWare ventricular assist system for bridge to transplant: combined results of the bridge to transplant and continued access protocol trial. J Heart Lung Transplant. 2013 Jul;32(7):675-83. doi: 10.1016/j.healun.2013.04.004. — View Citation

Slepian MJ, Sheriff J, Hutchinson M, Tran P, Bajaj N, Garcia JGN, Scott Saavedra S, Bluestein D. Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis. J Biomech. 2017 Jan 4;50:20-25. doi: 10.1016/j.jbiomech.2016.11.016. Epub 2016 Nov 10. — View Citation

Valerio L, Consolo F, Bluestein D, Tran P, Slepian M, Redaelli A, Pappalardo F. Shear-mediated platelet activation in patients implanted with continuous flow LVADs: A preliminary study utilizing the platelet activity state (PAS) assay. Annu Int Conf IEEE Eng Med Biol Soc. 2015 Aug;2015:1255-8. doi: 10.1109/EMBC.2015.7318595. — View Citation

Valerio L, Tran PL, Sheriff J, Brengle W, Ghosh R, Chiu WC, Redaelli A, Fiore GB, Pappalardo F, Bluestein D, Slepian MJ. Aspirin has limited ability to modulate shear-mediated platelet activation associated with elevated shear stress of ventricular assist devices. Thromb Res. 2016 Apr;140:110-117. doi: 10.1016/j.thromres.2016.01.026. Epub 2016 Feb 1. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events. Change of PAS assay from baseline to 24 months post-implant	Correlation between platelet activation and the development of post-implant complications	Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE
Primary	Number of participants with treatment-related adverse events. Change of TGT from baseline to 24-months post-implant	Correlation between platelet pro-thrombinase activity and the development of post-implant complications	Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE
Primary	Number of participants with treatment-related adverse events. Change of clinical and coagulation parameters from baseline to 24-months post-implant	Correlation between coagulation parameters and the development of post-implant complications	Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE
Primary	Number of participants with treatment-related adverse events. Change of pump working conditions after the device implant	Correlation between pump working conditions and the development of post-implant complications	Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE
Secondary	Number of participants with treatment-related adverse events. Change of prescribed antithrombotic therapy (anticoagulation and antiplatelet drugs) from baseline to 24 months post-implant	Correlation between antithrombotic therapy and the development of post-implant complications	Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE