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MACCE in Hospitalized Patients With Community-acquired Pneumonia

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ClinicalTrials.gov Identifier: NCT01773863
Recruitment Status : Recruiting
First Posted : January 23, 2013
Last Update Posted : September 17, 2018
Sponsor:
Information provided by (Responsible Party):
Francesco Violi, University of Roma La Sapienza

Tracking Information
First Submitted Date January 18, 2013
First Posted Date January 23, 2013
Last Update Posted Date September 17, 2018
Study Start Date October 2011
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 22, 2013)
Platelet activation, clotting abnormalities, myocardial damage and inflammation in CAP patients [ Time Frame: 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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: January 22, 2013)
Major adverse cardiac and cerebrovascular events [ Time Frame: 2 years ]
Major adverse cardiac and cerebrovascular events will be assessed during hospitalization and during the follow-up
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title MACCE in Hospitalized Patients With Community-acquired Pneumonia
Official Title Major Adverse Cardiac and Cerebrovascular Events in Hospitalized Patients With Community-acquired Pneumonia
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.

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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Plasma, serum and urine samples
Sampling Method Non-Probability Sample
Study Population Patients hospitalized for community-acquired pneumonia
Condition Community-acquired Pneumonia
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 27, 2016)
500
Original Estimated Enrollment
 (submitted: January 22, 2013)
250
Estimated Study Completion Date October 2020
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 95 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Francesco Violi, MD 064461933 ext +39 francesco.violi@uniroma1.it
Contact: Roberto Cangemi, MD 0649970103 ext +39 roberto.cangemi@uniroma1.it
Listed Location Countries Italy
Removed Location Countries  
 
Administrative Information
NCT Number NCT01773863
Other Study ID Numbers MACCE and CAP
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Francesco Violi, University of Roma La Sapienza
Study Sponsor University of Roma La Sapienza
Collaborators Not Provided
Investigators
Study Chair: Francesco Violi, MD Sapienza University of Rome
PRS Account University of Roma La Sapienza
Verification Date September 2018