Clinical trial NCT01492387: Duration of Antibiotic Therapy in Community - Acquired Pneumonia
Official title: Individualizing Duration of Antibiotic Therapy in Hospitalized Patients With Community - Acquired Pneumonia: a Non-inferiority, Randomized, Controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pneumonia
Bronchopneumonia
Pleuropneumonia
Pneumonia, Bacterial
Pneumonia, Viral
Keywords: community-acquired pneumonia
healthcare-associated pneumonia
antibiotic therapy
Duration of therapy
Lead sponsor: University of Milan
Sponsor class: OTHER
Collaborators: name: University of Milano Bicocca
First posted: 2011-12-15
Enrollment: 892
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the efficacy of an individualized approach to duration of antibiotic therapy based on each subject's clinical response compared to a local standard approach in patients coming from the community and who are hospitalized because of a pneumonia.


Eligibility criteria: Inclusion Criteria:

Patients will be 18 years old or older and meet all of the following inclusion criteria to be eligible for enrollment into the trial:

1. Diagnosis of pneumonia:

   Evidence of a new pulmonary infiltrate seen on either radiograph or computed tomography of the chest within 48 hours after hospitalization plus at least two among the following: 1) new or increased cough with/without sputum production and/or purulent respiratory secretions; 2) fever (documented temperature -rectal or oral- ≥ 37.8 °C) or hypothermia (documented temperature -rectal or oral- \<36o C); 3) deterioration of oxygenation; 4) evidence of systemic inflammation (such as abnormal white blood cell count -either leukocytosis (\>10,000/cm3) or leukopenia (\< 4,000/cm3) - or increasing of C-reactive protein or procalcitonin values above the local upper limit.

   CAP will be defined as pneumonia occurring in any patient admitted to the hospital coming from the community and who were not hospitalized in the previous 14 days. HCAP will be defined as a community-acquired pneumonia occurring in a patient with any of the following special epidemiological characteristics: patient who was hospitalized for 2 days or more in the previous 90 days; patient coming from a nursing home or extended care facility; patient who received home infusion therapy (including antibiotics) or wound care in the previous 30 days; patient who was on chronic dialysis in the previous 30 days.
2. An appropriate empiric antibiotic therapy for the pneumonia received within 24 hours after admission to the hospital.
3. A clinical stability reached within 5 days after hospital admission, in the absence of any changes of the initial empiric antibiotic therapy.
4. Signed informed consent

Exclusion Criteria:

Patients presenting with any of the following will not be included in the trial:

1. Patients with immunodeficiency, defined as: chemotherapy in the previous 12 months, radiotherapy in the previous 12 months, transplantation, immunosuppressive treatment, hematologic malignancy, AIDS or HIV with CD4 count \< 200, asplenia.
2. Patients with a concomitant infection on admission to the hospital requiring antibiotic therapy (i.e urinary tract infection). The presence of sepsis due to pneumonia will not be considered another concomitant infection.
3. Patients with documented bacteremia due to S. aureus in a blood culture (both methicillin resistant and susceptible S. aureus)
4. Patients with etiology of pneumonia due to fungi, mycobacterium or Pneumocystis jiroveci.
5. Patients hospitalized in the previous 15 days

Inclusion and exclusion criteria for the proposed study will not limit the study cohort on the basis of sex, ethnicity, socioeconomic status or other potentially discriminatory factors.

Primary outcomes:
measure: Composite outcome including adverse events
timeFrame: 30 days
Secondary outcomes:
measure: Composite outcome of other adverse events
timeFrame: 30 days
measure: Antibiotic exposure
timeFrame: 90 days
measure: Adverse effects
timeFrame: 90 days
measure: Composite outcome of other adverse events at 90 days
timeFrame: 90 days
measure: Length of hospitalization
timeFrame: 30 days
measure: Costs
timeFrame: 30 days
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: AO Ospedali Riuniti Bergamo
city: Bologna
country: Italy
facility: AO Policlinico S. Orsola Malpighi, University of Bologna
city: Como
country: Italy
facility: AO S. Anna
city: Genoa
country: Italy
facility: University of Genoa
city: Mantova
country: Italy
facility: AO C. Poma
city: Milan
country: Italy
facility: AO San Carlo Borromeo
city: Milan
country: Italy
facility: IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico
city: Milan
country: Italy
facility: Ospedale Luigi Sacco, University of Milan
city: Modena
country: Italy
facility: University of Modena e Reggio Emilia
city: Monza
country: Italy
facility: Univeristy of Milano Bicocca
city: Pavia
country: Italy
facility: IRCCS Policlinico S. Matteo, University of Pavia
city: Reggio Emilia
country: Italy
facility: AO S. Maria Nuova
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico di San Donato Milanese, University of Milan
city: Udine
country: Italy
facility: AO S. Maria della Misericordia,
Study officials:
affiliation: University of Milano Bicocca, Milan, Italy
name: Stefano Aliberti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Louisville, KY, USA
name: Julio A Ramirez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aliberti S, Blasi F, Zanaboni AM, Peyrani P, Tarsia P, Gaito S, Ramirez JA. Duration of antibiotic therapy in hospitalised patients with community-acquired pneumonia. Eur Respir J. 2010 Jul;36(1):128-34. doi: 10.1183/09031936.00130909. Epub 2009 Nov 19.
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: Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, Ortqvist A, Schaberg T, Torres A, van der Heijden G, Read R, Verheij TJ; Joint Taskforce of the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases. Guidelines for the management of adult lower respiratory tract infections--full version. Clin Microbiol Infect. 2011 Nov;17 Suppl 6(Suppl 6):E1-59. doi: 10.1111/j.1469-0691.2011.03672.x.