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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест PAS assay, TGT
  Evaluation of platelet function

Первичные конечные точки

• Number of participants with treatment-related adverse events. Change of PAS assay from baseline to 24 months post-implant [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE]

Вторичные конечные точки (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 [Срок оценки: Through study completion. Specific time-points: 1, 3, 6, 12, 18, and 24 months post-implant and at the occurrence of any AE]

Критерии участия

Критерии включения

• 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

Критерии исключения

\- Patients < 18-years old

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 1 центр

• San Raffaele Scientifc Institute - Cardiothoracic Intensive Care Unit — Milan

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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 Transpla PMID 23796152

Идентификаторы

NCT: NCT03255928 · PASVAD v. n°1 10/03/2017

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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