- The primary objective of the study is to demonstrate the non-inferiority in clinical
efficacy at the test of cure (TOC) visit planned 5-7 days after treatment completion of
levofloxacin 750 mg once daily (od) in comparison with piperacillin/tazobactam 4 g/500
mg every 8 hours in treating adult patients suffering from mild to moderate
hospital-acquired pneumonia.
Secondary Objectives:
The secondary objectives of the study are:
- To assess the clinical and bacteriological efficacy at the end of study (EOS) visit, 28
Inclusion Criteria:
Subjects meeting all of the following criteria will be considered for enrollment into the
study:
- General ward or ICU hospitalized subject.
- Subject with diagnosis of hospital-acquired pneumonia of presumed bacterial origin
based upon:
- Infection developing after at least 72 hours following hospital admission and
- At least three of the four following signs:
- Fever, defined as body temperature (oral or tympanic temperature ≥ 38°C or
rectal temperature ≥ 38. 5°C)
- Purulent tracheal sputum production/secretion or change in sputum character
- Total peripheral white blood cell (WBC) count > 12 G/L or < 4. 5 G/L or 15%
immature neutrophils (bands), regardless of total peripheral WBC count
- Increased plasma or serum C reactive protein (CRP) level as shown by a
level of at least twice the upper boundary of the hospital normal range and
- Chest X-ray findings (anterior posterior [AP] or posterior anterior [PA],
if possible lateral view) in agreement with the clinical diagnosis of
bacterial pneumonia, i. e. appearance of new, progressive pulmonary
infiltrate(s) attributable to infectious etiology.
- Subjects are required to have specimens collected for microbiological documentation
within 24 hours prior to enrolment. Specimens should include at least one invasive or
noninvasive lower respiratory tract specimen for Gram stain, culture and
susceptibility testing, and at least 2 venous blood samples for culture and
susceptibility testing.
Exclusion Criteria:
Subjects presenting with any of the following will not be included in the study:
Related to the hospital-acquired pneumonia (HAP):
- Suspected viral or fungal pneumonia, or HAP strongly suspected to be caused by MRSA
(methicillin-resistant Staphylococcus aureus) or organisms responsible for atypical
pneumonia, such as Chlamydia pneumoniae, Legionella pneumophila or Mycoplasma
pneumoniae
- Patients with severe HAP, defined as presence of at least one of the following:
- In previously non-ventilated patients: need for mechanical ventilation
consequently to HAP
- In previously ventilated patients: oxygenation rate defined by partial pressure
of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) < 200
- Radiographic findings compatible with severe HAP, i. e. showing either:
- Rapid progression (e. g. increase in the size of the opacity by ≥ 50% within 48
hours of the current evaluation)
- OR multilobar pneumonia (> 2 lobes) or involvement of both lungs
- OR cavitation of a lung infiltrate
- Evidence of severe sepsis with hypotension and/or end-organ dysfunction, i. e.:
- Shock commonly evidenced by: systolic blood pressure < 90 mmHg or diastolic
blood pressure < 60 mmHg
- In absence of previous vasopressors use, vasopressors use (except for fluid
replacement) for more than 4 hours
- In presence of vasopressors use, increase in vasopressors use (except for fluid
replacement) for more than 4 hours
- OR marked reduction in urine output (unless another explanation is available),
i. e. in 1 hour: < 20 mL or in 4 hours: < 80 mL
- OR acute renal failure requiring dialysis
- OR profound alteration of mental status, i. e. marked lethargy/stupor/coma
Related to medical history/concomitant conditions:
- Patients with any concomitant pulmonary diseases, conditions or complications that
could confound the interpretation or evaluation of drug efficacy or safety, including
severe bronchiectases, cystic fibrosis, active pulmonary tuberculosis or acute
pulmonary embolism, empyema, lung abscess or extra pulmonary extension of the LRTI
(lower respiratory tract infection), such as meningitis, septic arthritis,
endocarditis, known bronchial obstruction due to tumor or foreign body or with a
history of post-obstructive pneumonia (this does not exclude patients with COPD
[chronic obstructive pulmonary disease]), primary lung cancer or another malignancy
metastatic to the lungs, and/or requiring chemotherapeutic treatment (for this or
other reasons)
- Patients with any known or suspected bacterial infection other than the disease under
investigation which will require concomitant use of a systemic antimicrobial agent
other than the study drug allocated
- Patients who have received previous systemic antibiotics longer than 24 hours within
72 hours prior to the enrolment for the same episode of HAP
- Body weight > 95 kg
- Patients with impaired renal function, as shown by creatinine clearance < 20 mL/min
- Hepatic cirrhosis with Child-Pugh score > or = B
- Immuno-compromised patients, such as those presenting with either:
- Known HIV infection with a CD4 + T-lymphocyte count < 0. 2 G/L (i. e. < 200
cells/mm3)
- Neutropenia - neutrophil count < 1. 0 G/I (i. e. < 1000/mm3)
- Patients on maintenance (≥ 3 months) corticosteroid therapy (> 20 mg/day
equivalent prednisolone)
Related to study drugs:
- Patients with a microbiologically documented infection with a pathogen known prior to
inclusion to be resistant to at least one of the study medications
- Patients with known or suspected hypersensitivity to, or known or suspected serious
adverse reaction to levofloxacin and/or piperacillin/tazobactam and/or any other
quinolones, beta-lactamase inhibitors, penicillins and/or to cephalosporins
- Patients with epilepsy or a history of epilepsy or with predisposition to seizures
(e. g. patients with pre-existing central nervous system lesions)
- Patients with known or suspected history of tendon disorders unless a potential
relationship to fluoroquinolone administration has been excluded.
- Patients with latent or actual known defects in glucose-6-phosphate dehydrogenase
activity
General:
- Women who are breast-feeding, or are failing to use adequate contraception; for
example, systemic hormones (birth control pills, implant), intrauterine device or
barrier method (diaphragm with intravaginal spermicide, cervical cap, male or female
condom), or are pregnant, as demonstrated by urine or serum pregnancy tests carried
out before exposure to study medication or the start of any study procedure that
could pose a risk to the foetus
- Patients with a recent (within three months prior to study entry) history of drug or
alcohol abuse
- Patients who have received any investigational drug within one month prior to study
entry.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.
Sanofi-Aventis, Vienna, Austria
Sanofi-Aventis, Brussels, Belgium
Sanofi-Aventis, Prague, Czech Republic
Sanofi-Aventis, Paris, France
Sanofi-Aventis, Berlin, Germany
Sanofi-Aventis, Athens, Greece
Sanofi-Aventis, Guatemala, Guatemala
Sanofi-Aventis, Milan, Italy
Sanofi-Aventis, Beirut, Lebanon
Sanofi-Aventis, Mexico, Mexico
Sanofi-Aventis, Gouda, Netherlands
Sanofi-Aventis, Bucharest, Romania
Sanofi-Aventis, Moscow, Russian Federation
Sanofi-Aventis, Johannesburg, South Africa
Sanofi-Aventis, Barcelona, Spain
Sanofi-Aventis, Istanbul, Turkey
Sanofi-Aventis, Caracas, Venezuela
