Duration of Antibiotic Therapy in Community - Acquired Pneumonia (DURATION)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Pneumonia; Bronchopneumonia; Pleuropneumonia; Pneumonia, Bacterial; Pneumonia, Viral	Other: Discontinuation of antibiotic therapy	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	892 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Individualizing Duration of Antibiotic Therapy in Hospitalized Patients With Community - Acquired Pneumonia: a Non-inferiority, Randomized, Controlled Trial.
Study Start Date :	January 2012
Estimated Primary Completion Date :	December 2014
Estimated Study Completion Date :	March 2015

Arms and Interventions

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Arm	Intervention/treatment
No Intervention: Local standard of care; Patients randomized to this arm will be treated for the duration of therapy dictated by the primary care physician.
Experimental: Individualized arm; Patients randomized to this arm will be treated according to clinical response: antibiotic therapy will be discontinued 48 hours after the day that the patient reaches clinical stability, with at least 5 days of total antibiotic treatment.	Other: Discontinuation of antibiotic therapy; Patients randomized in the Individualized Arm will be treated according to clinical response: antibiotic therapy will be discontinued 48 hours after the day that the patient reaches clinical stability, with at least 5 days of total antibiotic treatment.

Outcome Measures

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Primary Outcome Measures :

1. Composite outcome including adverse events [ Time Frame: 30 days ]
   Any among the following: 1) disease-specific complications due to pneumonia, such as lung abscess, empyema, meningitis, endocarditis, arthritis or pericarditis; 2) clinical failure during hospitalization (either hemodynamic or respiratory failure); 3) a new course of antibiotics (at least one dose), after discontinuation of antibiotic therapy given for the pneumonia, either endovenous or oral; 4) re-hospitalization; 5) death.

Secondary Outcome Measures :

1. Composite outcome of other adverse events [ Time Frame: 30 days ]
   Any among the following: 1) disease-specific complications due to pneumonia, such as lung abscess, empyema, meningitis, endocarditis, arthritis or pericarditis; 2) clinical failure due to pneumonia occurring during hospitalization (either hemodynamic or respiratory failure); 3) a new course of antibiotics (at least one dose), after discontinuation of antibiotic therapy given for the pneumonia, either endovenous or oral, for a relapse of pneumonia; 4) re-hospitalization due to a relapse of pneumonia; 5) death due to pneumonia.
2. Antibiotic exposure [ Time Frame: 90 days ]
   Days of antibiotic exposure, including intravenous and oral antibiotic therapy given for any reason.
3. Adverse effects [ Time Frame: 90 days ]
   Adverse effects will include: anaphylactic reactions and allergic skin reactions; Clostridium difficile-associated colitis; hematologic toxicity; hepatotoxicity; convulsions; tendinopathies; peripheral neuropathy; prolongation of the QTc interval; nausea; diarrhea; vomiting; abdominal pain; nephrotoxicity.
4. Composite outcome of other adverse events at 90 days [ Time Frame: 90 days ]
   Any among the following: 1) a new course of antibiotics for any reason after discontinuation of antibiotic therapy for pneumonia; 2) re-hospitalization for any reason; 3) death from any reason.
5. Length of hospitalization [ Time Frame: 30 days ]
   Number of days from the date of admission to the hospital to either the date of discharge (patients sent home or to a long-term care facility) or the date of death if occurred during hospitalization.
6. Costs [ Time Frame: 30 days ]
   Costs of care differences between the two study groups based on the total length of hospital stay.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Contacts

Contact: Stefano Aliberti, MD	00393394171538	stefano.aliberti@unimib.it
Contact: Francesco Blasi, MD		francesco.blasi@unimi.it

Locations

Italy
AO Ospedali Riuniti Bergamo	Not yet recruiting
Bergamo, Italy
Contact: Giovanni Michetti, MD gmichetti@ospedaliriuniti.bergamo.it
AO Policlinico S. Orsola Malpighi, University of Bologna	Recruiting
Bologna, Italy
Contact: Pierluigi Viale, MD pierluigi.viale@unibo.it
Principal Investigator: Stefano Nava, MD
AO S. Anna	Recruiting
Como, Italy
Contact: Anna Rosa Maspero, MD anna.maspero@hsacomo.org
University of Genoa	Not yet recruiting
Genoa, Italy
Contact: Claudio Viscoli, MD claudio.viscoli@unige.it
AO C. Poma	Not yet recruiting
Mantova, Italy
Contact: Carlo Sturani, MD carlo.sturani@aopoma.it
AO San Carlo Borromeo	Recruiting
Milan, Italy
Contact: Sandro Amaducci, MD amaducci.sandro@sancarlo.mi.it
IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico	Recruiting
Milan, Italy
Contact: Francesco Blasi, MD francesco.blasi@unimi.it
Sub-Investigator: Roberto Cosentini, MD
Ospedale Luigi Sacco, University of Milan	Recruiting
Milan, Italy
Contact: Nicola Montano, MD nicola.montano@unimi.it
Principal Investigator: Fabio Franzetti, MD
University of Modena e Reggio Emilia	Not yet recruiting
Modena, Italy
Contact: Luca Richeldi, MD luca.richeldi@unimore.it
Univeristy of Milano Bicocca	Recruiting
Monza, Italy
Contact: Stefano Aliberti, MD stefano.aliberti@unimib.it
Principal Investigator: Stefano Aliberti, MD
Sub-Investigator: Andrea Gori, MD
IRCCS Policlinico S. Matteo, University of Pavia	Not yet recruiting
Pavia, Italy
Contact: Maurizio Luisetti, MD m.luisetti@smatteo.pv.it
AO S. Maria Nuova	Recruiting
Reggio Emilia, Italy
Contact: Luigi Zucchi, MD zucchi.luigi@asmn.re.it
Istituto Clinico Humanitas	Not yet recruiting
Rozzano, Italy
Contact: Antonio Voza, MD antonio.voza@humanitas.it
IRCCS Policlinico di San Donato Milanese, University of Milan	Recruiting
San Donato Milanese, Italy
Contact: Vincenzo Valenti, MD vincenzo.valenti@unimi.it
AO S. Maria della Misericordia,	Not yet recruiting
Udine, Italy
Contact: Paolo Rossi, MD rossi.paolo@aoud.sanita.fvg.it
Principal Investigator: Matteo Bassetti, MD

Sponsors and Collaborators

University of Milan

University of Milano Bicocca

Investigators

Principal Investigator:	Stefano Aliberti, MD	University of Milano Bicocca, Milan, Italy
Principal Investigator:	Julio A Ramirez, MD	University of Louisville, KY, USA

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Related Info 

Publications:

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.

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:S27-72.

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:E1-59. doi: 10.1111/j.1469-0691.2011.03672.x.

Responsible Party:	Francesco Blasi, Professor, University of Milan
ClinicalTrials.gov Identifier:	NCT01492387 History of Changes
Other Study ID Numbers:	DURATION
First Posted:	December 15, 2011
Last Update Posted:	January 3, 2014
Last Verified:	December 2013

Keywords provided by Francesco Blasi, University of Milan:

community-acquired pneumonia; healthcare-associated pneumonia; antibiotic therapy; Duration of therapy

Additional relevant MeSH terms:

Pneumonia; Pneumonia, Bacterial; Pneumonia, Viral; Pleuropneumonia; Bronchopneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Bacterial Infections	Virus Diseases; Pleurisy; Pleural Diseases; Bronchial Diseases; Anti-Bacterial Agents; Antibiotics, Antitubercular; Anti-Infective Agents; Antitubercular Agents