Duration of Antibiotic Therapy in Community - Acquired Pneumonia

Pneumonia Clinical Trial

— DURATION  

Official title:

Individualizing Duration of Antibiotic Therapy in Hospitalized Patients With Community - Acquired Pneumonia: a Non-inferiority, Randomized, Controlled Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01492387
• Other study ID #: DURATION
• Status: Recruiting
• Phase: Phase 4
• First received: December 5, 2011
• Last updated: December 31, 2013
• Start date: January 2012
• Est. completion date: March 2015

Study information

• Verified date: December 2013
• Source: University of Milan
• Contact: Stefano Aliberti, MD
• Phone: 00393394171538
• Email: stefano.aliberti[@]unimib.it
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 892
• Est. completion date: March 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alveolitis, Extrinsic Allergic
• Bronchopneumonia
• Pleuropneumonia
• Pneumonia
• Pneumonia, Bacterial
• Pneumonia, Viral

Intervention

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.

Locations

Country	Name	City	State
Italy	AO Ospedali Riuniti Bergamo	Bergamo
Italy	AO Policlinico S. Orsola Malpighi, University of Bologna	Bologna
Italy	AO S. Anna	Como
Italy	University of Genoa	Genoa
Italy	AO C. Poma	Mantova
Italy	AO San Carlo Borromeo	Milan
Italy	IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico	Milan
Italy	Ospedale Luigi Sacco, University of Milan	Milan
Italy	University of Modena e Reggio Emilia	Modena
Italy	Univeristy of Milano Bicocca	Monza
Italy	IRCCS Policlinico S. Matteo, University of Pavia	Pavia
Italy	AO S. Maria Nuova	Reggio Emilia
Italy	Istituto Clinico Humanitas	Rozzano
Italy	IRCCS Policlinico di San Donato Milanese, University of Milan	San Donato Milanese
Italy	AO S. Maria della Misericordia,	Udine

Sponsors (2)

Lead Sponsor	Collaborator
University of Milan	University of Milano Bicocca

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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. — View 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:S27-72. — View 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:E1-59. doi: 10.1111/j.1469-0691.2011.03672.x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite outcome including adverse events	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.	30 days	No
Secondary	Composite outcome of other adverse events	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.	30 days	No
Secondary	Antibiotic exposure	Days of antibiotic exposure, including intravenous and oral antibiotic therapy given for any reason.	90 days	No
Secondary	Adverse effects	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.	90 days	Yes
Secondary	Composite outcome of other adverse events at 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.	90 days	No
Secondary	Length of hospitalization	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.	30 days	No
Secondary	Costs	Costs of care differences between the two study groups based on the total length of hospital stay.	30 days	No