A Phase 3, Randomized Double-Blind Study of Ceftobiprole Medocaril Versus Linezolid Plus Ceftazidime in the Treatment of Nosocomial Pneumonia - CHOPIN-1

• Conditions: osocomial Pneumonia; MedDRA version: 9.1Level: LLTClassification code 10052596Term: Nosocomial pneumonia

• Registration Number: EUCTR2004-001730-17-LT
• Lead Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2004-10-11
• Last Update Posted: 11 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 770

Inclusion Criteria

1) Written informed consent provided. Consent may be given for unconscious/ incapacitated subjects by their next of kin, guardian or legal representative according to local regulatory and ethical practice using a patient information sheet and informed consent form approved by the responsible Ethics Committee.
2) Male or female patients aged = 18 years.
3) Femal subjects must be postmenopausal (for at least 1 year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of of pregnancy), or practicing an effective method of birth control (e.g. prescription oral contraceptives, contraceptive injections or patch, intrauterine device, double-barrier method (e.g. condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), male partner sterilization or, at the discretion of the investigator, abstinence), before entry and throughout the study; and have a negative serum or urine pregnancy test (depending on local regulations) at screning.
4) Subject suffering from NP or VAP defined as follows:
Nosocomial Pneumonia (subject must have a, b, c and d)
a) Clinical diagnosis of pneumonia after a minimum of 72 hours of hospitalization or in a chronic care facility
Excemptions would include:
- =48 to <72 hours of hospitalization or in a chronic care facility if at admission no acute inflammatory pulmonary infiltrate was present, WBC and differential blood count was normal, and the reason for admission was not an infection, OR
- discharge from hospital or chronic care facility =48 hours after a stay of =72 hours
b) Clinical signs or symptoms of pneumonia with AT LEAST 2 of the following criteria:
- New onset of purulent sputum production or respiratory secretions or a worsening in character of sputum.
- Tachypnea (respiratory rate =20/minute), particularly if progressive in nature.
- Hypoxemia with a P02=60 mmHg while subject is breathing on room air, as determined by pulse oximetry or arterial blood gas, or alveoloar arterial O2 gradient, or respiratory failure requiring mechanical ventilation.
c) New or persistent (persistance is defined as the infiltrate being radiographically visible for at least 72 Hours) radiographic infiltrates (not related to another disease process)
d) Fever or leukocytosis/leukopenia consistent with a diagnosis of pneumonia with AT LEAST 1 of the follosing:
- Fever ((in the absence of anti-pyretics), increase in core temperature of >1°C OR an oral temperature >38°C, a tympanic temperature >38.5°C, a rectal/core temperature >39°C, OR hypothermia, defined as a rectal/core body temperature of <35°C)
- Leukocytosis (a total WBC count =10 x 10exp9/L or =15% immature neutrophils (bands), regardless of total peripheral white count; or leucopenia with total WBC =4.5 x 10exp9/L )
Ventilator- Associated Pneumonia
Subjects with NP (as defined above) who developed pneumonia more than 48 hours after onset of mechanical ventilation.
5) Microbiological samples (respiratory secretions) suitable for culture and microscopy.
6) APACHE II score = 8 and = 25.
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

1) Female patients who are pregnant or lactating.
2) Known or suspected hypersensitivity to any related antiinfective (including beta-lactam antibiotics such as penicillins, cephalosporins, oxazolidinone, or monobactams)
3) Any known or suspected condition or concurrent treatment that would be contraindicated by the prescribing information for linezolid (any medicinal product which inhibits monoamine oxidases A or B, [e.g., phenelzine, isocarboxazid, selegiline, moclobemide] or within 2 weeks of taking any such medicinal product) or ceftazidime. Exception: Subjects with underlying conditions and/or on concomitant medications that might put them at risk from MAO inhibition can only be enrolled if they are hospitalized.
4) Known or suspected severe renal impairment, (calculated creatinine clearance [CrCl] < 30 mL/minute, or oliguria < 20 mL/h unresponsive to fluid challenge) or any form of dialysis.
5) Known or suspected hepatic dysfunction (total bilirubin, or alanine aminotransferase [ALT], or aspartate aminotransferase [AST] = 3 x upper limit of the normal range [ULN]).
6) Previous criterion no longer applicable.
7)Previous enrollment in this study.
8) Treatment with any investigational drug within 30 days before enrollment.
9) Any other known or suspected condition of the patient that may jeopardize adherence to protocol requirements (e.g.severe chronic obstructive pulmonary disease [COPD], NYHA Class 4 cardiac disease, burn subjects with >15% total body burn or any significant third degree burn).
10) Known to be HIV-positive with CD4 counts of =0.2x10exp9/L (=200 cells/mm³). Subjects with HIV and >0.2x10exp9/L [>200 cells/mm³] may be included).
11) Presence of myelosuppression or neutropenia (absolute neutrophil count [ANC] =0.5x10exp9/L [<500 PMNs/mm³]), severe anemia (hemoglobin <6.5 g/dL), or severe thrombocytopenia (<49.9x10exp9/cm). Note; subjects receiving immunosuppressive therapy who are expected to reach a nadir of <500PMNs/mm³ during administration of study drug should not be enrolled.
12) Children or other family members of the investigator or of emplyees of the study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center.

Clinical conditions that may interfere with assessment of efficacy:
13) Sustained shock (e.g., systolic BP < 90 mmHg for > 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents).
14) Subjects with either- known bronchial obstruction or a history of post-obstructive pneumonia (mild and moderate chronic obstructive pulmonary disease [COPD] patients are allowed) including primary lung cancer or another malignancy metastatic to the lungs, - cystic fibrosis, - lung abscess, - pleural effusion as a primary source of infection- active tuberculosis, or - subjects requiring antibiotic cover for aspiration pneumonia, atypical pneumonia (including Legionella pneumophila) or Pneumocystis jiroveci (carinii) pneumonia.

Microbiological conditions that may interfere with assessment of efficacy:
15) Systemic antimicrobial therapy for > 24 hours in the 48 hours before enrollment
Exceptions:Systemic antimicrobial therapy for more than 24 hours in the 48 hours before enrollment is permitted in case of any of the following: a) the infection is caused by microbiologically-confirmed pathogens that are resistant to the previous antimicrobial agents. b) the subject is clinically failing treatmen

Study & Design

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