Ignite Creation Date:
2024-05-06 @ 1:18 AM
Last Modification Date:
2024-10-26 @ 11:02 AM
Study NCT ID:
NCT01773863
Status:
UNKNOWN
Last Update Posted:
2021-09-30
First Post:
2013-01-18
Brief Title:
MACCE in Hospitalized Patients With Community-acquired Pneumonia
Sponsor:
University of Roma La Sapienza
Organization:
University of Roma La Sapienza
Study Overview
Official Title:
Major Adverse Cardiac and Cerebrovascular Events in Hospitalized Patients With Community-acquired Pneumonia
Status:
UNKNOWN
Status Verified Date:
2021-09
Last Known Status:
RECRUITING
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:
None
Brief Summary:
Community-acquired pneumonia is the most common infection leading to hospitalization in intensive care units and the most common cause of death associated with infection disease
Epidemiological studies have shown that respiratory tract infections are associated with an increased risk for the development of acute cardiovascular and cerebrovascular events
This link is further supported by studies indicating that influenza vaccination is associated with a reduced risk of hospitalization for pneumonia as well as heart disease and cerebrovascular disease
Data connecting acute respiratory tract infections and cardiovascular events stem almost exclusively from cross-sectional or retrospective studies Thus the real incidence and the prognostic impact of AMI as well as the pathophysiological relationship between pneumonia and cardiovascular damage is still elusive
Inflammation plays a major role in the pathogenesis of coronary artery disease The increased concentrations of proinflammatory cytokines together with the activation of coagulation the down-regulation of anticoagulant mechanisms and the enhanced platelet aggregation may trigger atheromas instability plaque rupture and thrombus formation
Inflammation and coagulopathy are also considered universal host responses to infection in patients with severe sepsis Thus far limited data are available on the changes in these high regulated systems together with platelet activity in patients with CAP and their potential relationship with cardiovascular risk
This project will consist in a prospective multicenter study to investigate the incidence of major adverse cardiac and cerebrovascular events MACCE in hospitalized patients with CAP its prognostic relevance and the potential relationship between enhanced cardiovascular risk and the activation of inflammation coagulation and platelet aggregation in this setting
Epidemiological studies have shown that respiratory tract infections are associated with an increased risk for the development of acute cardiovascular and cerebrovascular events
This link is further supported by studies indicating that influenza vaccination is associated with a reduced risk of hospitalization for pneumonia as well as heart disease and cerebrovascular disease
Data connecting acute respiratory tract infections and cardiovascular events stem almost exclusively from cross-sectional or retrospective studies Thus the real incidence and the prognostic impact of AMI as well as the pathophysiological relationship between pneumonia and cardiovascular damage is still elusive
Inflammation plays a major role in the pathogenesis of coronary artery disease The increased concentrations of proinflammatory cytokines together with the activation of coagulation the down-regulation of anticoagulant mechanisms and the enhanced platelet aggregation may trigger atheromas instability plaque rupture and thrombus formation
Inflammation and coagulopathy are also considered universal host responses to infection in patients with severe sepsis Thus far limited data are available on the changes in these high regulated systems together with platelet activity in patients with CAP and their potential relationship with cardiovascular risk
This project will consist in a prospective multicenter study to investigate the incidence of major adverse cardiac and cerebrovascular events MACCE in hospitalized patients with CAP its prognostic relevance and the potential relationship between enhanced cardiovascular risk and the activation of inflammation coagulation and platelet aggregation in this setting
Detailed Description:
Community-acquired pneumonia CAP is the most common infection leading to hospitalization in intensive care units and the most common cause of death associated with infection disease
Epidemiological studies have shown that respiratory tract infections are associated with an increased risk for the development of acute cardiovascular and cerebrovascular events
This link is further supported by studies indicating that influenza vaccination is associated with a reduced risk of hospitalization for pneumonia as well as heart disease cerebrovascular disease and the risk of death from all causes during influenza seasons in elderly
Data connecting acute respiratory tract infections and cardiovascular events stemmed almost exclusively from cross-sectional or retrospective studies and the pathophysiological relationship between pneumonia and cardiovascular damage is still elusive
The first aim of the study will be to analyze the prevalence of major adverse cardiac and cerebrovascular events MACCE in patients hospitalized for CAP followed up for two years after hospitalization
During hospitalization myocardial damage will be strictly monitored by measuring cardiac troponins until discharge
Cardiac troponins are established markers of myocardial damage Cardiac troponin elevation is seen not only in the setting of acute coronary syndromes but also in a variety of conditions not directly related to flow-limiting coronary stenosis or occlusion of the coronary arteries such as pulmonary embolism sepsis heart failure and stroke In these settings it is well documented that elevated circulating levels of troponins are associated with poor prognosis regardless of underlying disease
Sparse information exists concerning the significance of troponin elevation during respiratory tract infections Most of the studies investigated the role of troponin elevation in patients admitted in hospital for acutely exacerbated chronic obstructive pulmonary disease COPD only a recent study investigates specifically CAP showing a correlation between troponin elevation and oxygenation impairment however the underlying mechanism was not explored
Inflammation plays a major role in the pathogenesis of coronary artery disease The increased concentrations of proinflammatory cytokines together with the activation of coagulation the down-regulation of anticoagulant mechanisms and the enhanced platelet aggregation may trigger atheromas instability plaque rupture and thrombus formation
Systemic coagulation abnormalities including clotting activation and inhibition of anticoagulant factors have been observed in patients with severe sepsis in patients with CAP similar changes have been detected only in the lung compartment Changes of clotting system activation are of potential relevance as they could elicit myocardial damage with several mechanisms including coronary ischemia andor direct inflammation of cardiac cells Concerning this last point it is of interest that Protein C an anticoagulant factor with anti-inflammatory property is reduced in severe sepsis where it correlates with disease severity and mortality Accordingly infusion of recombinant human activated Protein C improves survival of patients with severe sepsis due to pneumococcal pneumonia
Until now no data exists about the behavior of Protein C in patients with CAP and its interplay with myocardial damage
Moreover no data on platelet reactivity and activation during pneumonia exist Very limited data is only available on common viral respiratory tract infections in which enhanced platelet reactivity has been shown
The investigators speculated that inhibition of Protein C as well as enhanced platelet activity may be implicated in myocardial damage in patients with CAP Therefore the investigators will perform a prospective study to investigate whether this relationship exist
Data obtained could have important clinical consequences new therapeutic strategies targeting these systems could prevent myocardial damage and eventually MACCEs in these patients
Epidemiological studies have shown that respiratory tract infections are associated with an increased risk for the development of acute cardiovascular and cerebrovascular events
This link is further supported by studies indicating that influenza vaccination is associated with a reduced risk of hospitalization for pneumonia as well as heart disease cerebrovascular disease and the risk of death from all causes during influenza seasons in elderly
Data connecting acute respiratory tract infections and cardiovascular events stemmed almost exclusively from cross-sectional or retrospective studies and the pathophysiological relationship between pneumonia and cardiovascular damage is still elusive
The first aim of the study will be to analyze the prevalence of major adverse cardiac and cerebrovascular events MACCE in patients hospitalized for CAP followed up for two years after hospitalization
During hospitalization myocardial damage will be strictly monitored by measuring cardiac troponins until discharge
Cardiac troponins are established markers of myocardial damage Cardiac troponin elevation is seen not only in the setting of acute coronary syndromes but also in a variety of conditions not directly related to flow-limiting coronary stenosis or occlusion of the coronary arteries such as pulmonary embolism sepsis heart failure and stroke In these settings it is well documented that elevated circulating levels of troponins are associated with poor prognosis regardless of underlying disease
Sparse information exists concerning the significance of troponin elevation during respiratory tract infections Most of the studies investigated the role of troponin elevation in patients admitted in hospital for acutely exacerbated chronic obstructive pulmonary disease COPD only a recent study investigates specifically CAP showing a correlation between troponin elevation and oxygenation impairment however the underlying mechanism was not explored
Inflammation plays a major role in the pathogenesis of coronary artery disease The increased concentrations of proinflammatory cytokines together with the activation of coagulation the down-regulation of anticoagulant mechanisms and the enhanced platelet aggregation may trigger atheromas instability plaque rupture and thrombus formation
Systemic coagulation abnormalities including clotting activation and inhibition of anticoagulant factors have been observed in patients with severe sepsis in patients with CAP similar changes have been detected only in the lung compartment Changes of clotting system activation are of potential relevance as they could elicit myocardial damage with several mechanisms including coronary ischemia andor direct inflammation of cardiac cells Concerning this last point it is of interest that Protein C an anticoagulant factor with anti-inflammatory property is reduced in severe sepsis where it correlates with disease severity and mortality Accordingly infusion of recombinant human activated Protein C improves survival of patients with severe sepsis due to pneumococcal pneumonia
Until now no data exists about the behavior of Protein C in patients with CAP and its interplay with myocardial damage
Moreover no data on platelet reactivity and activation during pneumonia exist Very limited data is only available on common viral respiratory tract infections in which enhanced platelet reactivity has been shown
The investigators speculated that inhibition of Protein C as well as enhanced platelet activity may be implicated in myocardial damage in patients with CAP Therefore the investigators will perform a prospective study to investigate whether this relationship exist
Data obtained could have important clinical consequences new therapeutic strategies targeting these systems could prevent myocardial damage and eventually MACCEs in these patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None