Duration of Antibiotic Therapy in Community - Acquired Pneumonia

Phase 4

• Conditions: Pneumonia; Bronchopneumonia; Pleuropneumonia; Pneumonia, Bacterial; Pneumonia, Viral
• Interventions: Other: Discontinuation of antibiotic therapy

• Registration Number: NCT01492387
• Lead Sponsor: University of Milan

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-05
• Study First Submitted QC: 2011-12-14
• Study First Posted: 2011-12-15
• Study Start: 2012-01
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-31
• Last Update Posted: 2014-01-03
• Primary Completion: 2014-12
• Study Completion: 2015-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 892

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Individualized arm	Discontinuation of antibiotic therapy	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.

Primary Outcome Measures

Name	Time	Method
Composite outcome including adverse events	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

Name	Time	Method
Antibiotic exposure	90 days	Days of antibiotic exposure, including intravenous and oral antibiotic therapy given for any reason.
Composite outcome of other adverse events at 90 days	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.
Length of hospitalization	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.
Costs	30 days	Costs of care differences between the two study groups based on the total length of hospital stay.
Composite outcome of other adverse events	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.
Adverse effects	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.

Trial Locations

Locations (15)

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

Ospedale Luigi Sacco, University of Milan; 🇮🇹 Milan, Italy

University of Modena e Reggio Emilia; 🇮🇹 Modena, Italy

Univeristy of Milano Bicocca; 🇮🇹 Monza, Italy

AO S. Maria Nuova; 🇮🇹 Reggio Emilia, Italy

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Italy

AO S. Maria della Misericordia,; 🇮🇹 Udine, Italy

IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico; 🇮🇹 Milan, Italy

IRCCS Policlinico S. Matteo, University of Pavia; 🇮🇹 Pavia, Italy

IRCCS Policlinico di San Donato Milanese, University of Milan; 🇮🇹 San Donato Milanese, Italy