Community-acquired PneumoniaNCT01773863
MACCE in Hospitalized Patients With Community-acquired Pneumonia
An observational study of Community-acquired Pneumonia, run by University of Roma La Sapienza at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Community-acquired Pneumonia
- How many people
- 500 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2011to Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients hospitalized for community-acquired pneumonia
Who may be able to join
- community-acquired pneumonia
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Internal and Medical Specialities Department - Policlinico Umberto I
Rome, 00162
Francesco Violi, MD, 064461933 ext. +39, francesco.violi@uniroma1.it
Roberto Cangemi, MD, 0649970103, roberto.cangemi@uniroma1.it
About this study
Official title: Major Adverse Cardiac and Cerebrovascular Events in Hospitalized Patients With Community-acquired Pneumonia
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.
Read more
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.
Read the 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.
- Conditions
- Community-acquired Pneumonia
- Keywords
- Community-acquired pneumonia, Acute myocardial infarction, Platelet activation, Coagulation abnormalities,, Thrombosis, Isoprosantes, NADPH oxidase, Major adverse cardiac and cerebrovascular events
- Medical subject headings
- Community-Acquired Pneumonia, Thrombosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet activation, clotting abnormalities, myocardial damage and inflammation in CAP patients
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
Measured: 2 years
Secondary outcomes (1)
Major adverse cardiac and cerebrovascular events
Major adverse cardiac and cerebrovascular events will be assessed during hospitalization and during the follow-up
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2013 (estimated)
- Study startOct 2011
- Primary completionApr 2021
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Community-acquired PneumoniaStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Violi, University of Roma La Sapienza
- Investigators
- Francesco Violi, MD, Study chair, University of Roma La SapienzaRoberto Cangemi, MD, Principal investigator, University of Roma La SapienzaRoberto Cangemi, Study director, Sapienza - Unviersity of Rome
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01773863
- Sponsor's protocol ID
- MACCE and CAP
- Status last verified
- Sep 2021
- First submitted
- 18 Jan 2013
- Last updated
- 30 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cangemi R, Calvieri C, Bucci T, Carnevale R, Casciaro M, Rossi E, Calabrese CM, Taliani G, Grieco S, Falcone M, Palange P, Bertazzoni G, Celestini A, Pignatelli P, Violi F; SIXTUS study group. Is NOX2 upregulation implicated in myocardial injury in patients with pneumonia? Antioxid Redox Signal. 2014 Jun 20;20(18):2949-54. doi: 10.1089/ars.2013.5766. Epub 2014 Mar 14.
PubMed 24328853Cangemi R, Casciaro M, Rossi E, Calvieri C, Bucci T, Calabrese CM, Taliani G, Falcone M, Palange P, Bertazzoni G, Farcomeni A, Grieco S, Pignatelli P, Violi F; SIXTUS Study Group; SIXTUS Study Group. Platelet activation is associated with myocardial infarction in patients with pneumonia. J Am Coll Cardiol. 2014 Nov 4;64(18):1917-25. doi: 10.1016/j.jacc.2014.07.985. Epub 2014 Oct 27.
PubMed 25444147Cangemi R, Calvieri C, Falcone M, Bucci T, Bertazzoni G, Scarpellini MG, Barilla F, Taliani G, Violi F; SIXTUS Study Group. Relation of Cardiac Complications in the Early Phase of Community-Acquired Pneumonia to Long-Term Mortality and Cardiovascular Events. Am J Cardiol. 2015 Aug 15;116(4):647-51. doi: 10.1016/j.amjcard.2015.05.028. Epub 2015 May 22.
PubMed 26089009Violi F, Carnevale R, Calvieri C, Nocella C, Falcone M, Farcomeni A, Taliani G, Cangemi R; SIXTUS study group. Nox2 up-regulation is associated with an enhanced risk of atrial fibrillation in patients with pneumonia. Thorax. 2015 Oct;70(10):961-6. doi: 10.1136/thoraxjnl-2015-207178. Epub 2015 Jun 29.
PubMed 26123660Pastori D, Menichelli D, Romiti GF, Speziale AP, Pignatelli P, Basili S, Violi F, Cangemi R. Prediction of new-onset atrial fibrillation with the C2HEST score in patients admitted with community-acquired pneumonia. Infection. 2024 Aug;52(4):1539-1546. doi: 10.1007/s15010-024-02286-x. Epub 2024 May 3.
PubMed 38700657Cangemi R, Carnevale R, Nocella C, Calvieri C, Bartimoccia S, Frati G, Pignatelli P, Picchio V, Violi F. Low-grade endotoxemia is associated with cardiovascular events in community-acquired pneumonia. J Infect. 2024 Feb;88(2):89-94. doi: 10.1016/j.jinf.2023.11.010. Epub 2023 Nov 23.
PubMed 38000675
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Major Adverse Cardiac and Cerebrovascular Events in Hospitalized Patients With Community-acquired Pneumonia
- ClinicalTrials.gov ID
- NCT01773863
- Acronym / sponsor ID
- MACCE and CAP
- Conditions
- Community-acquired Pneumonia
- Keywords
- Community-acquired pneumonia, Acute myocardial infarction, Platelet activation, Coagulation abnormalities,, Thrombosis, Isoprosantes, NADPH oxidase, Major adverse cardiac and cerebrovascular events
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- Oct 2011 (actual)
- Primary completion
- Apr 2021 (actual)
- Study completion
- Dec 2022 (estimated)
- First posted
- 23 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients hospitalized for community-acquired pneumonia
Key inclusion criteria (1 listed)
- community-acquired pneumonia
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
1 secondary outcome
Major adverse cardiac and cerebrovascular events
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2021.
- Results publication: PubMed 24328853Cangemi R, Calvieri C, Bucci T, Carnevale R, Casciaro M, Rossi E, Calabrese CM, Taliani G, Grieco S, Falcone M, Palange P, Bertazzoni G, Celestini A, Pignatelli P, Violi F; SIXTUS study group. Is NOX2 upregulation implicated in myocardial injury in patients with pneumonia? Antioxid Redox Signal. 2014 Jun 20;20(18):2949-54. doi: 10.1089/ars.2013.5766. Epub 2014 Mar 14.
- Results publication: PubMed 25444147Cangemi R, Casciaro M, Rossi E, Calvieri C, Bucci T, Calabrese CM, Taliani G, Falcone M, Palange P, Bertazzoni G, Farcomeni A, Grieco S, Pignatelli P, Violi F; SIXTUS Study Group; SIXTUS Study Group. Platelet activation is associated with myocardial infarction in patients with pneumonia. J Am Coll Cardiol. 2014 Nov 4;64(18):1917-25. doi: 10.1016/j.jacc.2014.07.985. Epub 2014 Oct 27.
- Results publication: PubMed 26089009Cangemi R, Calvieri C, Falcone M, Bucci T, Bertazzoni G, Scarpellini MG, Barilla F, Taliani G, Violi F; SIXTUS Study Group. Relation of Cardiac Complications in the Early Phase of Community-Acquired Pneumonia to Long-Term Mortality and Cardiovascular Events. Am J Cardiol. 2015 Aug 15;116(4):647-51. doi: 10.1016/j.amjcard.2015.05.028. Epub 2015 May 22.
- Results publication: PubMed 26123660Violi F, Carnevale R, Calvieri C, Nocella C, Falcone M, Farcomeni A, Taliani G, Cangemi R; SIXTUS study group. Nox2 up-regulation is associated with an enhanced risk of atrial fibrillation in patients with pneumonia. Thorax. 2015 Oct;70(10):961-6. doi: 10.1136/thoraxjnl-2015-207178. Epub 2015 Jun 29.
- Derived from this study: PubMed 38700657Pastori D, Menichelli D, Romiti GF, Speziale AP, Pignatelli P, Basili S, Violi F, Cangemi R. Prediction of new-onset atrial fibrillation with the C2HEST score in patients admitted with community-acquired pneumonia. Infection. 2024 Aug;52(4):1539-1546. doi: 10.1007/s15010-024-02286-x. Epub 2024 May 3.
- Derived from this study: PubMed 38000675Cangemi R, Carnevale R, Nocella C, Calvieri C, Bartimoccia S, Frati G, Pignatelli P, Picchio V, Violi F. Low-grade endotoxemia is associated with cardiovascular events in community-acquired pneumonia. J Infect. 2024 Feb;88(2):89-94. doi: 10.1016/j.jinf.2023.11.010. Epub 2023 Nov 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Violi, MD study chair
University of Roma La Sapienza
Roberto Cangemi, MD principal investigator
University of Roma La Sapienza
Roberto Cangemi study director
Sapienza - Unviersity of Rome
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Community-acquired Pneumonia, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Francesco Violi, MD (064461933 ext. +39, francesco.violi@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet activation, clotting abnormalities, myocardial damage and inflammation in CAP patients (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01773863, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2021.