E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
TO COMPARE THE CLINICAL OUTCOME FOLLOWING TREATMENT WITH CEFTOBIPROLE VERSUS LINEZOLID PLUS CEFTAZIDIME IN PATIENTS WITH NP. |
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E.2.2 | Secondary objectives of the trial |
To compare the microbiological outcome following treatment with ceftobiprole VERSUS or linezolid plus ceftazidime in patients with NP . - To compare the clinical and microbiological outcome by pathogen following treatment with ceftobiprole VERSUS or linezolid plus ceftazidime in patients with NP. - To compare the clinical AND MICROBILOGICAL outcome following treatment with ceftobiprole VERSUS or linezolid plus ceftazidime in patients with VAP. - TO COMPARE THE 30 DAY PNEUMONIA SPECIFIC MORTALITY RATES FOLLOWING TREATMENT WITH CEFTOBIPROLE VERSUS LINEZOLID PLUS CEFTAZIDIME IN PATIENTS WITH NP - To compare duration of stay in high care ward (e.g. intensive care unit [ICU]) following treatment with ceftobiprole VERSUS or linezolid plus ceftazidime in patients with NP. - To characterize the safety and tolerability of treatment with ceftobiprole in patients with NP.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Written informed consent provided. Consent may be given for unconscious/ incapacitated patients 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) Patients who, in the opinion of the investigator, require antibiotic therapy with anti-MRSA antibiotic activity. 4) Patients suffering from NP or VAP defined as follows:
NOSOCOMIAL PNEUMONIA a) CLINICAL DIAGNOSIS OF PNEUMONIA AFTER ● A MINIMUM OF 72 HOURS OF HOSPITALISATION OR IN A CHRONIC CARE FACILITY ● ≥ 48 TO < 72 HOURS OF HOSPITALISATION OR INA 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. ● DISCHARGE FROM HOSPITAL R CHRONIC CARE FACILITY ≤ 48 HOURS AFTER A STAY OF ≥ 72 HOURS
WITH AT LEAST TWO (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 ANY OR ALL OF THESE ARE PROGRESSIVE IN NATURE. • HYPOXEMIA WITH A P02 < 60 MMHG WHILE PATIENT 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. b) NEW OR PERSISTENT RADIOGRAPHIC INFILTRATES (NOT RELATED TO ANOTHER DISEASE PROCESS) IN CONJUNCTION WITH AT LEAST ONE OF THE FOLLOWING: ● FEVER (IN THE ABSENCE OF ANTI-PYRETICS), INCREASE IN CORE TEMPERATURE OF > 1ºC OR AN ORAL TEMPERATURE >38C, A TYMPANIC TEMPERATURE >38.5C, A RECTAL/CORE TEMPERATURE >39C, OR HYPOTHERMIA, DEFINED AS A RECTAL/CORE BODY TEMPERATURE OF <35C. ● LEUKOCYTOSIS (25% INCREASE IN CIRCULATING LEUKOCYTES FROM BASELINE AND A TOTAL WBC COUNT ≥10 X 109/L OR ≥15% IMMATURE NEUTROPHILS (BANDS), REGARDLESS OF TOTAL PERIPHERAL WHITE COUNT; OR LEUCOPENIA WITH TOTAL WBC< 4.5X 109/L.
2,Persistence is defined as the infiltrate being radiographically visible for at leaset 72 hours
Ventilator- Associated Pneumonia PATIENTS WHO DEVELOP NOSOCOMIAL PNEUMONIA (AS DEFINED ABOVE) MORE THAN 48 HOURS AFTER ONSET OF MECHANICAL VENTILATON 5) Microbiological samples(RESPIRATORY SECRETION) suitable for culture. 6) APACHE II score ≥ 8 and ≤ 25.
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E.4 | Principal exclusion criteria |
General 1) Female PATIENTS who are pregnant or lactating. 2) Women of childbearing potential unable or unwilling to USE AN EFFECTIVE METHOD OF BIRTH CONTROL 3) KNOW OR SUSPECTED Hypersensitivity to any study medication (including lactam antibiotics such as penicillins, cephalosporins, oxazolidinone, or monobactams) 4) Any KNOW OR SUSPECTED condition or concurrent treatment contraindicated by the prescribing information for linezolid or ceftazidime. 5) KNOW 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. 6) KNOW OR SUSPECTED Hepatic dysfunction (total bilirubin, or alanine aminotransferase [ALT], or aspartate aminotransferase [AST] 3 x upper limit of the normal range [ULN]). 7) Previous enrollment in this study. 8) Treatment with any investigational drug within 30 days before enrollment. 9) Any other KNOW OR SUSPECTED condition of the patient that may jeopardize adherence to protocol requirements.
Clinical conditions that may interfere with assessments of efficacy 10) Sustained shock (e.g. systolic blood pressure [BP] <90 mmHg for >2 hours despite FLUID RESUSCITATION WITH EVIDENCE OF HYPOPERFUSION OR NEED FOR SYMPATHOMIMETIC AGENTS. 11) Patients with either - known bronchial obstruction or a history of post-obstructive pneumonia (chronic obstructive pulmonary disease [COPD] patients are allowed) including primary lung cancer or another malignancy metastatic to the lungs, - cystic fibrosis, - lung abscess, - infected pleural effusion - active tuberculosis, or - patients requiring antibiotic cover for aspiration pneumonia, atypical pneumonia or Pneumocystis jiroveci (carinii) pneumonia. 12) KNOWN OR SUSPECTED Neutropenic subjects (absolute neutrophil count [ANC] 0.5x109/L), 13) KNOWN OR SUSPECTED patients with CD4 counts 0.2x109/L.
Microbiological conditions that may interfere with assessment of efficacy: 13) Systemic antimicrobial therapy for more than 24 hours in the 7 days prior to enrollment Systemic antimicrobial therapy for > 24 hours is permitted in case: a) the infection is caused by microbiologically-confirmed pathogens that are resistant to the previous antimicrobial agents. b) the patient is clinically deteriorating despite at least 72 hours of treatment. 14) Evidence from available surveillance cultures of (co-)infection with pathogen(s) such as: - ESBL producers, - Proteus vulgaris and - Ceftazidime- or ceftobiprole-resistant non-fermenters
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E.5 End points |
E.5.1 | Primary end point(s) |
Cure, failure, not evaluable |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |