MACCE in Hospitalized Patients With Community-acquired Pneumonia

Sponsor
University of Roma La Sapienza (Other)
Overall Status
Recruiting
CT.gov ID
NCT01773863
Collaborator
(none)
500
1
134
3.7

Study Details

Study Description

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 atheroma's 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.

Condition or Disease Intervention/Treatment Phase

    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 atheroma's 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 and/or 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 Design

    Study Type:
    Observational
    Anticipated Enrollment :
    500 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Major Adverse Cardiac and Cerebrovascular Events in Hospitalized Patients With Community-acquired Pneumonia
    Actual Study Start Date :
    Oct 1, 2011
    Actual Primary Completion Date :
    Apr 1, 2021
    Anticipated Study Completion Date :
    Dec 1, 2022

    Outcome Measures

    Primary Outcome Measures

    1. Platelet activation, clotting abnormalities, myocardial damage and inflammation in CAP patients [2 years]

      Platelet and serum thromboxane, F2-isoprostanes, NOX2-activation, serum high-sensitivity cardiac troponin T, protein C and protein S at hospital admission and at hospital discharge

    Secondary Outcome Measures

    1. Major adverse cardiac and cerebrovascular events [2 years]

      Major adverse cardiac and cerebrovascular events will be assessed during hospitalization and during the follow-up

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 95 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • community-acquired pneumonia
    Exclusion Criteria:
    • presence of immunosuppression (HIV infection, high dose of immunosuppressive agents such as prednisone, chemotherapy);

    • presence of malignancy;

    • pregnancy or breast feeding;

    • health care-associated pneumonia

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Internal and Medical Specialities Department - Policlinico Umberto I Rome Italy 00162

    Sponsors and Collaborators

    • University of Roma La Sapienza

    Investigators

    • Study Chair: Francesco Violi, MD, Sapienza University of Rome
    • Principal Investigator: Roberto Cangemi, MD, Sapienza University of Rome
    • Study Director: Roberto Cangemi, Sapienza - Unviersity of Rome

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Francesco Violi, Director, Head of Internal Medicine, Clinical Professor, University of Roma La Sapienza
    ClinicalTrials.gov Identifier:
    NCT01773863
    Other Study ID Numbers:
    • MACCE and CAP
    First Posted:
    Jan 23, 2013
    Last Update Posted:
    Sep 30, 2021
    Last Verified:
    Sep 1, 2021
    Keywords provided by Francesco Violi, Director, Head of Internal Medicine, Clinical Professor, University of Roma La Sapienza
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 30, 2021