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

NCT03255928 | Recruiting FDA Device

• 1 other identifier: PASVAD v. n°1 10/03/2017
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Platelet activation; Ventricular Assist Device; Thrombosis; Bleeding; Antithrombotic Pharmacological Therapy; Mechanical Circulatory Support

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (1)

• Number of participants with treatment-related adverse events. Change of prescribed antithrombotic therapy (anticoagulation and antiplatelet drugs) from baseline to 24 months post-implant

  Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE

Study Arms (2)

VAD-implanted patients

All patients receiving a VAD implant

Diagnostic Test: PAS assay, TGT

VAD-patients suffering adverse events (AE)

VAD-patients sustaining a thromboembolic/bleeding complication over the course of support

Diagnostic Test: PAS assay, TGT

Interventions

PAS assay, TGT DIAGNOSTIC_TEST

Evaluation of platelet function

VAD-implanted patients; VAD-patients suffering adverse events (AE)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with end-stage heart failure receiving a mechanical circulatory support system

You may qualify if:

• 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

You may not qualify if:

• \- Patients \< 18-years old

Sponsors & Collaborators

• Scientific Institute San Raffaele: lead
• Università Vita-Salute San Raffaele: collaborator

Study Sites (1)

San Raffaele Scientifc Institute - Cardiothoracic Intensive Care Unit

Milan, MI, 20132, Italy

RECRUITING

Related Publications (16)

• 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.

  PMID: 26736495 BACKGROUND

• 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.

  PMID: 28694489 BACKGROUND

• 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.

  PMID: 24043375 BACKGROUND

• 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.

  PMID: 20135353 BACKGROUND

• 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.

  PMID: 10405294 BACKGROUND

• 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.

  PMID: 27887727 BACKGROUND

• 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.

  PMID: 28146651 BACKGROUND

• 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.

  PMID: 23796152 BACKGROUND

• 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.

  PMID: 26938158 BACKGROUND

• 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.

  PMID: 29282819 BACKGROUND

• 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.

  PMID: 29362190 BACKGROUND

• 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.

  PMID: 29952802 BACKGROUND

• Foglieni C, Ravanelli D, Lombardi M, Spartano L, Pieri M, Ajello S, Landoni G, Scandroglio AM, Consolo F. Platelet microRNA Expression Can Predict Bleeding in HeartMate3 Patients Treated With or Without Aspirin. J Cardiovasc Transl Res. 2025 Oct;18(5):1032-1041. doi: 10.1007/s12265-025-10659-2. Epub 2025 Jul 11.

  PMID: 40643853 DERIVED

• Consolo F, Pieri M, Pazzanese V, Scandroglio AM, Pappalardo F. Longitudinal analysis of pump parameters over long-term support with the HeartMate 3 left ventricular assist device. J Cardiovasc Med (Hagerstown). 2023 Oct 1;24(10):771-775. doi: 10.2459/JCM.0000000000001522. Epub 2023 Jun 30.

  PMID: 37409664 DERIVED

• Consolo F, Marasi A, Della Valle P, Bonora M, Pieri M, Scandroglio AM, Redaelli A, Zangrillo A, D'Angelo A, Pappalardo F. Bleeding in patients with continuous-flow left ventricular assist devices: acquired von Willebrand disease or antithrombotics? Eur J Cardiothorac Surg. 2022 Jun 15;62(1):ezab474. doi: 10.1093/ejcts/ezab474.

  PMID: 34718493 DERIVED

• Consolo F, Pappalardo F. Real-Time Analysis of the Log Files of the HeartWare Continuous-Flow Left Ventricular Assist Device for the Early Diagnosis of Pump Thrombosis: a Step Forward Toward Clinical Translation. J Cardiovasc Transl Res. 2022 Apr;15(2):408-415. doi: 10.1007/s12265-021-10157-1. Epub 2021 Jul 19.

  PMID: 34282539 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Platelet-free-plasma

MeSH Terms

Conditions

Thrombosis; Blood Coagulation Disorders; Hemorrhage

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Filippo Consolo, PhD

  San Raffaele Scientific Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Filippo Consolo, PhD

CONTACT

+390226436153; consolo.filippo@unisr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 28, 2017
• First Posted: August 21, 2017
• Study Start: June 29, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)