Randomized, Double-Blind, Multicenter Study of Ceftobiprole Medocaril Versus Ceftriaxone with/without Linezolid in Treatment of Subjects Hospitalized With Community-Acquired Pneumonia - CAP

• Conditions: Hospitalized community acquired pneumonia; MedDRA version: 8.1Level: LLTClassification code 10010120Term: Community acquired pneumonia

• Registration Number: EUCTR2006-000835-84-DE
• Lead Sponsor: Jansen-Cilag International N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-06-30
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 670

Inclusion Criteria

- Men or women, 18 years of age or older

- Women must be postmenopausal (for at least 1 year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method [e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel], contraceptive patch, male partner sterilization) before entry and continue to use the same method of contraception throughout the study

- Women must have a negative serum ß-human chorionic gonadotropin
(b-hCG) or urine pregnancy test (depending on local regulations) before enrollment

- Willing to adhere to the prohibitions and restrictions specified in this protocol

- Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Disease Specific
Subjects with CAP severe enough to require hospitalization and treatment with i.v. antibiotics for at least 3 days (72 hours) defined as follows:

Subjects must have a, b, c, d, AND e

a) Clinical diagnosis of acute bacterial pneumonia acquired in the community. Subjects must have resided in the community (i.e., NOT in a chronic care facility such as a nursing home or rehabilitation facility) and NOT have been hospitalized during the 14 days before the onset of symptoms of pneumonia. Residence in an assisted-living facility where the subject has regular access to the community is allowed.

b) Clinical signs or symptoms of acute bacterial pneumonia with AT LEAST 2 of the following criteria:
-Cough (new or increased over usual state)
-Production of purulent sputum or a worsening in the character of sputum
-Auscultatory findings on pulmonary examination of rales or evidence of pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony)
-Dyspnea or tachypnea (respiratory rate ³20 breaths per minute), that is new or worse than usual state
-New onset hypoxemia on room air (PO2 <60 mmHg on arterial blood gas or O2 saturation <90% by pulse oximetry), or respiratory failure requiring mechanical ventilation.

c) New radiographic infiltrates (not related to another disease process) consistent with the diagnosis of bacterial pneumonia

d) Fever or leukocytosis/leukopenia (temporally associated with the onset of pneumonia symptoms) with AT LEAST 1 of the following:
- Fever (in the absence of antipyretics) defined as an axillary temperature >37.5°C, oral temperature >38°C, a tympanic temperature >38.5°C, a rectal temperature >39°C, OR hypothermia, defined as a rectal body temperature of <35°C
- Leukocytosis defined as an elevated total peripheral WBC count ³10 x 109/L or ³15% immature neutrophils (bands), regardless of total peripheral white count; OR leukopenia with total WBC £4.5 x 109/L.

e) Severity of pneumonia requiring intravenous antibiotic therapy.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Potential subjects who meet any of the following criteria will be excluded from participating in the study:

- History of or suspected condition that may jeopardize adherence to protocol requirements (e.g., severe cardiac disease such that even minimal physical activity causes discomfort, New York Heart Association [NYHA] Class 4)44

- History of or suspected hypersensitivity to any related anti-infective (including beta lactam antibiotics such as penicillins and cephalosporins, oxazolidinones). Subjects in whom cephalosporins would be used as part of normal clinical practice are not excluded.

- History of or suspected condition or concurrent treatment that would be contraindicated by the prescribing information for ceftriaxone or linezolid

- History of or suspected severe renal impairment, (i.e., ClCr £30 mL/min or oliguria <20 mL/h unresponsive to fluid challenge) or any form of dialysis

- History of or suspected hepatic dysfunction (total bilirubin, or alanine aminotransferase [ALT], or aspartate aminotransferase [AST] ³3 times the upper limit of the normal range [ULN]).

- History of suspected extra-pulmonary infection, including concomitant meningitis, endocarditis, septic arthritis, or osteomyelitis

- Known to be human immunodeficiency virus (HIV) positive with CD4 counts of £0.2x109/L (£200 cells/mm3). (Subjects with HIV and >0.2x109/L [>200 cells/mm3] may be included)

- Presence of neutropenia, (absolute neutrophil count [ANC] £0.5x109/L [<500 Neutrophils [polymorphonuclear leukocytes] [PMNs/mm3]) severe anemia (hemoglobin <6.5 g/dL), or severe thrombocytopenia (<49.9x109/cm)
Note: Subjects receiving immunosuppressive therapy who are expected to reach a nadir of <500 PMNs/mm3 during administration of study drug should not be enrolled

- Previous enrollment in this study or any other ceftobiprole protocol

- Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment

- Is pregnant or breast-feeding

- Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator

Clinical conditions that may interfere with assessments of efficacy:
·Sustained shock
·Subjects with any of the following pulmonary conditions:

–known bronchial obstruction or a history of postobstructive pneumonia
–primary lung cancer or another malignancy to the lungs unless surgically resected
–cystic fibrosis
–lung abscess
–pleural effusion as a primary source of infection
–active tuberculosis
–suspected or known pneumonia due to aspiration, atypical bacteria (Legionella spp, Mycoplasma pneumoniae, and Chlamydia pneumoniae), viruses, or Pneumocystis jiroveci (carinii).

Microbiological conditions that may interfere with assessments of efficacy:

· Systemic antimicrobial therapy for more than 24 hours in the 3 days before enrollment.

Exception: Systemic antimicrobial therapy for more than 24 hours is permitted in case of a subject with an infection caused by microbiologically confirmed pathogen(s) that are resistant to the previous antimicrobial agents (e.g., pneumonia due to a macrolide resistant staphylococci or pneumococci being treated with a macrolide).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified