Ignite Creation Date:
2024-07-17 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06487091
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-05
First Post:
2024-05-31
Brief Title:
Platelet Function and Impella Support
Sponsor:
Università Vita-Salute San Raffaele
Organization:
Università Vita-Salute San Raffaele
Study Overview
Official Title:
Analysis of Platelet Function During Impella Support
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMPELLA-PLT
Brief Summary:
Mechanical circulatory support MCS with the Impella microaxial pump in the setting of cardiogenic shockcardiac arrest CSCA is accompanied by substantial risk of life-threatening complications including hemolysis thrombotic and bleeding events
Previous studies in patients on durable MCS suggest that device-induced platelet dysfunction plays a major contributory role in the development of such events and that selected markers of platelet function have the potential to stratify patients according to an elevated risk of adverse events To date the potential clinical utility of markers of altered platelet function in patients supported with an Impella pump is unexplored
The proposed study will analyze changes in platelet function in the setting of Impella support primary aim and possibly identify a platelet function profile indicative of patients at high-risk to develop adverse events secondary aim
The study is a prospective observational study Changes in the expression levels of markers of both platelet activation and aggregation in patients supported with an Impella pump will be measured Data will be longitudinally measured pre-implant before Impella implantation and then after 24 48 and 72h of Impella support Markers that will be analyzed include surface platelet receptors and platelet microRNAs Experimental data will be correlated with clinical outcomes including the occurrence of adverse events
This study will provide mechanistic insights into the effect of Impella support on the protein and miRNA expression of platelets The intention is to get a better understanding of distinct pathways of platelet function related to Impella support and their relationship to adverse events Our data might open the perspective for the future clinical use of markers of platelet function to enhance the early recognition of patients at high risk of developing an adverse event and the definition of novel personalized therapeutic strategies targeted to platelet biology to prevent their occurrence
Previous studies in patients on durable MCS suggest that device-induced platelet dysfunction plays a major contributory role in the development of such events and that selected markers of platelet function have the potential to stratify patients according to an elevated risk of adverse events To date the potential clinical utility of markers of altered platelet function in patients supported with an Impella pump is unexplored
The proposed study will analyze changes in platelet function in the setting of Impella support primary aim and possibly identify a platelet function profile indicative of patients at high-risk to develop adverse events secondary aim
The study is a prospective observational study Changes in the expression levels of markers of both platelet activation and aggregation in patients supported with an Impella pump will be measured Data will be longitudinally measured pre-implant before Impella implantation and then after 24 48 and 72h of Impella support Markers that will be analyzed include surface platelet receptors and platelet microRNAs Experimental data will be correlated with clinical outcomes including the occurrence of adverse events
This study will provide mechanistic insights into the effect of Impella support on the protein and miRNA expression of platelets The intention is to get a better understanding of distinct pathways of platelet function related to Impella support and their relationship to adverse events Our data might open the perspective for the future clinical use of markers of platelet function to enhance the early recognition of patients at high risk of developing an adverse event and the definition of novel personalized therapeutic strategies targeted to platelet biology to prevent their occurrence
Detailed Description:
STUDY DESIGN AND MAIN OBJECTIVE Prospective observational study to evaluate changes in the expression levels of markers of platelet function activation and aggregation capacity in CSCA patients who receive an Impella device for temporary mechanical circulatory support
HYPOTHESIS
progressive change of platelet function occurs over the course of Impella support driven by shear forces exerted by the pump on recirculating blood
markers of changes in platelet function can be identified at the protein and nuclear level in platelet samples extracted form patients supported with an Impella pump
specific trends of the changes of the expression levels of markers of platelet function might allow identifying patients at higher risk of developing a thrombotichemorrhagic complication
the expression levels of markers of platelet function are indeed altered in patients even before the clinical manifestation of the event
METHODOLOGY The markers that will be analyzed have been selected according to recent studies showing
significant changes in their expression levels driven by durable MCS devices
their potential to identify patients at high risk of developing adverse events
their association with coagulationhemostatic disorders and hemolysis and include
platelet receptors GPIba GPIIbIIIa and GPVI 1-4
platelet microRNA miR-20b-5p miR-25-3p miR-126-5p miR-451a miR-320a miR-223-3p miR-144-rp miR-151a-3p and miR-454-3p 5 The expression levels of these microRNAs will be measured in both PRP and PPP samples to confirm their actual expression by platelets
Data will be measured
pre-implant ie immediately prior to Impella implantation to evaluate the patient-specific baseline profile and then following
24 hours 48 hours and 72 hours of Impella support This way it will possible to quantify longitudinal changes in the levels of expression of the selected markers over the course of Impella support vs baseline
Data will be also measured during the acute phase of any of the following adverse events that will occur during Impella support not limited to 72 hours
thrombosis of the patient - any site - and of the pump
ischemichemorrhagic stroke
any surgical or non-surgical bleeding
hemolysis Adverse events will be defined according to most recent criteria 6-8
Furthermore inferences of any change in the anticaogulation regimen that may occur over the course of Impella support not limited to 72 hours will be evaluated to this aim markers of platelet function will be analyzed 12 hours following any change in the anticoagulation regimen
Experimental data will be correlated with clinical outcomes including the occurrence of adverse events to possibly identify an event-related platelet function profile characteristics of the sub-group of patients that will develop adverse events The occurrence of adverse events will be continuously recorded over the whole duration of Impella support
TREATMENT PROCEDURE To measure the expression levels of the selected markers of platelet function platelet samples will be isolated from patients blood 10-mL volume via standard laboratory techniques The expression levels of the analyzed markers will be measured via quantitative real-time polymerase chain reaction and protein quantitationfunction assay such as enzyme-linked immunosorbent assay
HYPOTHESIS
progressive change of platelet function occurs over the course of Impella support driven by shear forces exerted by the pump on recirculating blood
markers of changes in platelet function can be identified at the protein and nuclear level in platelet samples extracted form patients supported with an Impella pump
specific trends of the changes of the expression levels of markers of platelet function might allow identifying patients at higher risk of developing a thrombotichemorrhagic complication
the expression levels of markers of platelet function are indeed altered in patients even before the clinical manifestation of the event
METHODOLOGY The markers that will be analyzed have been selected according to recent studies showing
significant changes in their expression levels driven by durable MCS devices
their potential to identify patients at high risk of developing adverse events
their association with coagulationhemostatic disorders and hemolysis and include
platelet receptors GPIba GPIIbIIIa and GPVI 1-4
platelet microRNA miR-20b-5p miR-25-3p miR-126-5p miR-451a miR-320a miR-223-3p miR-144-rp miR-151a-3p and miR-454-3p 5 The expression levels of these microRNAs will be measured in both PRP and PPP samples to confirm their actual expression by platelets
Data will be measured
pre-implant ie immediately prior to Impella implantation to evaluate the patient-specific baseline profile and then following
24 hours 48 hours and 72 hours of Impella support This way it will possible to quantify longitudinal changes in the levels of expression of the selected markers over the course of Impella support vs baseline
Data will be also measured during the acute phase of any of the following adverse events that will occur during Impella support not limited to 72 hours
thrombosis of the patient - any site - and of the pump
ischemichemorrhagic stroke
any surgical or non-surgical bleeding
hemolysis Adverse events will be defined according to most recent criteria 6-8
Furthermore inferences of any change in the anticaogulation regimen that may occur over the course of Impella support not limited to 72 hours will be evaluated to this aim markers of platelet function will be analyzed 12 hours following any change in the anticoagulation regimen
Experimental data will be correlated with clinical outcomes including the occurrence of adverse events to possibly identify an event-related platelet function profile characteristics of the sub-group of patients that will develop adverse events The occurrence of adverse events will be continuously recorded over the whole duration of Impella support
TREATMENT PROCEDURE To measure the expression levels of the selected markers of platelet function platelet samples will be isolated from patients blood 10-mL volume via standard laboratory techniques The expression levels of the analyzed markers will be measured via quantitative real-time polymerase chain reaction and protein quantitationfunction assay such as enzyme-linked immunosorbent assay
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None