Clinical trial NCT01143155: Failure and Cardiovascular Events in Community-acquired Pneumonia
Official title: Clinical Failure and Cardiovascular Events in Hospitalized Patients With Community-Acquired Pneumonia: The Failcap Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Community-acquired Pneumonia
Keywords: Pneumonia
Community-acquired pneumonia
Healthcare-associated pneumonia
Failure
Cardiovascular events
Outcome
Lead sponsor: University of Milan
Sponsor class: OTHER
First posted: 2010-06-14
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive patients admitted to any of the study centers will be screened for study entry. Patients with a diagnosis of community-acquired pneumonia (including those with health-care associated pneumonia) will be evaluated to define study entry criteria

Brief summary: Although failure and mortality are the most relevant outcomes in patients with Community-acquired Pneumonia (CAP), there is little discussion in the literature on their incidence and etiology. A pathophysiological approach has been recently developed and used to evaluate clinical failure in CAP patients. Clinical failure has been analyzed as related versus unrelated to CAP, considering the role that the pulmonary infection and the inflammatory response played in the development of this outcome. Cardiac events were identified as triggers of clinical failures in a significant percentage of CAP patients. The development of cardiovascular events have been also identified in CAP patients both on admission to the hospital and during hospitalization. However, data on this topic belong to studies evaluating only selected populations of veteran patients with CAP. Understanding clinical failure, as well as cardiovascular events in hospitalized patients with CAP would be useful in order to prevent complications during the hospitalization, to develop new treatment modalities and, thus, to improve outcomes.

The objectives of this international, multicenter, observational, prospective cohort study will be: 1) To define incidence, timing, etiology and risk factors of clinical failure, related vs. unrelated to CAP, in hospitalized patients with CAP; 2) To define incidence, timing, and risk factors for cardiovascular events either on hospital admission or during hospitalization in hospitalized patients with CAP.Consecutive adult patients hospitalized for CAP in acute care hospitals in Europe and US will be enrolled. Daily clinical evaluations. Demographics, history, clinical, radiological, and antibiotic therapy data will be recorded, as well as serum, urinary and respiratory samples will be collected both on admission and during hospitalization from consenting individuals. Patients will be classified as having a CAP-related versus CAP-unrelated failure, according to a pathophysiological classification. Patients will be also classified as having or not a cardiovascular event either on admission or during hospitalization.The following outcomes will be measured:

1) Incidence, timing, etiology and risk factors of clinical failure related vs. unrelated to CAP; 2) Incidence, timing and risk factors of cardiovascular events; 3)time to clinical stability, length of hospital stay, mortality at hospital discharge, and mortality at 30 and 180 days.


Eligibility criteria: Inclusion Criteria:

1) Signed inform consent to participate in the study

2) Criteria for community-acquired pneumonia:

1. New pulmonary infiltrate seen on chest radiograph or CT Scan of the chest within 48 hours after hospitalization.

   plus at least one of the following:
2. New or increased cough with/without sputum production
3. Fever (documented temperature -rectal or oral- \> 38.3 or hypothermia (documented temperature -rectal or oral- \< 36 C)
4. Evidence of systemic inflammation (such as abnormal white blood cell count -either leukocytosis (\> 10,000/cm3) or leukopenia (\< 4,000/cm3) - or C-reactive protein (CRP) or procalcitonin (PCT) values above the local upper limit.

3) Patients with a diagnosis of healthcare-associated pneumonia (HCAP) will be included in the study and a secondary analysis will performed on this subgroup of patients.

Exclusion Criteria:

Patients who meet at least one of the following definitions will be excluded from the analysis:

1. Patient has hospital-acquired pneumonia, defined as pneumonia that develops after 48 hours of the current hospitalization, or pneumonia that develops in a patient who had been discharged from the hospital within the prior 14 days of the current hospitalization.
2. Patient is re-admitted with a new episode of pneumonia during the 14-day follow up period from the previous hospitalization.
3. Unstable psychiatric or psychological condition rendering the subject unlikely to be cooperative or to complete the study requirements.
4. Subject history that in the investigator's opinion would preclude subject compliance with the protocol.

Primary outcomes:
measure: Clinical failure
timeFrame: 30 days
Secondary outcomes:
measure: Cardiovascular event
timeFrame: 30 days
measure: Time to clinical stability
timeFrame: 7 days
measure: Length of hospital stay
timeFrame: 30 days
measure: In-hospital mortality
timeFrame: 30 days
measure: Adverse events after hospital discharge
timeFrame: up to 180 days after hospital discharge
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Dipartimento toraco-polmonare e cardio-circolatorio, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study officials:
affiliation: Dipartimento toraco-polmonare e cardio-circolatorio, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
name: Francesco Blasi, M.D., PhD
role: STUDY_DIRECTOR
affiliation: Respiratory Department, AO San Gerardo, University of Milan-Bicocca, Monza, Italy
name: Stefano Aliberti, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Infectious Diseases, Department of Medicine, University of Louisville, Louisville, Kentucky, USA
name: Julio Ramirez, M.D.
role: STUDY_DIRECTOR
affiliation: Emergency Medicine Department, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
name: Roberto Cosentini, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: UO Pneumologia, IRCCS Policlinico San Donato, University of Milan, Milan, Italy
name: Vincenzo Valenti, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: UO Medicina d'Urgenza, Istituto Clinico Humanitas; Milan, Italy
name: Antonio Voza, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: UO Pneumologia, Ospedale "Luigi Sacco", University of Milan, Milan, Italy
name: Delfino Legnani, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinica Pneumologia, Azienda Ospedaliera S. Gerardo di Monza, University of Milano-Bicocca, Monza, Italy
name: Alberto Pesci, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Respiratory Disease, University of Modena and Reggio Emilia, Modena, Italy
name: Luca Richeldi, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinic of Pneumology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland
name: Daiana Stolz, M.D., MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Infectious Diseases, University of Louisville, KY; USA
name: Paula Peyrani, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, Dean N, File T, Fine MJ, Gross PA, Martinez F, Marrie TJ, Plouffe JF, Ramirez J, Sarosi GA, Torres A, Wilson R, Yu VL; American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001 Jun;163(7):1730-54. doi: 10.1164/ajrccm.163.7.at1010. No abstract available.
citation: Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2(Suppl 2):S27-72. doi: 10.1086/511159. No abstract available.
citation: Aliberti S, Amir A, Peyrani P, Mirsaeidi M, Allen M, Moffett BK, Myers J, Shaib F, Cirino M, Bordon J, Blasi F, Ramirez JA. Incidence, etiology, timing, and risk factors for clinical failure in hospitalized patients with community-acquired pneumonia. Chest. 2008 Nov;134(5):955-962. doi: 10.1378/chest.08-0334. Epub 2008 Jun 26.
citation: Ramirez J, Aliberti S, Mirsaeidi M, Peyrani P, Filardo G, Amir A, Moffett B, Gordon J, Blasi F, Bordon J. Acute myocardial infarction in hospitalized patients with community-acquired pneumonia. Clin Infect Dis. 2008 Jul 15;47(2):182-7. doi: 10.1086/589246.
citation: Musher DM, Rueda AM, Kaka AS, Mapara SM. The association between pneumococcal pneumonia and acute cardiac events. Clin Infect Dis. 2007 Jul 15;45(2):158-65. doi: 10.1086/518849. Epub 2007 Jun 6.
citation: Jasti H, Mortensen EM, Obrosky DS, Kapoor WN, Fine MJ. Causes and risk factors for rehospitalization of patients hospitalized with community-acquired pneumonia. Clin Infect Dis. 2008 Feb 15;46(4):550-6. doi: 10.1086/526526.
citation: Mortensen EM, Coley CM, Singer DE, Marrie TJ, Obrosky DS, Kapoor WN, Fine MJ. Causes of death for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team cohort study. Arch Intern Med. 2002 May 13;162(9):1059-64. doi: 10.1001/archinte.162.9.1059.