A Safety and Tolerability Study of Doripenem Compared with Cefepime in Hospitalized Children with Bacterial Pneumonia

• Conditions: Bacterial Pneumonia; MedDRA version: 14.1Level: LLTClassification code 10004051Term: Bacterial pneumonia, unspecifiedSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2009-016069-27-LT
• Lead Sponsor: Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-22
• Last Update Posted: 2 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1 - Have new or progressive radiographic infiltrate(s) (alveolar, lobar, or consolidation) consistent with a bacterial pneumonia that is not related to cardiac or other disease processes. (Note: subjects with clinically significant pleural effusions may be included if an empyema has been ruled out by a diagnostic sampling of pleural fluid. Chest X-rays obtained within 48 hours before the start of the infusion of the first dose of IV study drug therapy are acceptable for the screening examination. A computed tomography (CT) scan/magnetic resonance imaging (MRI) may be used to supplement a chest X-ray if the chest X-ray is not sufficiently interpretable).
2 - Have a clinical presentation compatible with bacterial pneumonia with ALL of the
following:
o Fever (oral temperature >38.0C, tympanic temperature >38.3C, or rectal or core temperature >38.8C) or hypothermia (rectal or core temperature <35.0C) AND
o Leukocytosis defined as WBC count > or = 15,000 cells/µL OR > or = 15% immature neutrophils, regardless of the total peripheral white cell count OR neutrophil count >1.2 times (x) the upper limit of normal (ULN); OR leucopenia with total WBC count <4500 cells/µL AND
o Non-intubated subjects must have at least 2 of the following clinical signs or symptoms:
– Cough
– New onset of LRT secretions, change in character of secretions, or increase in the quantity of secretions or suctioning requirements
– Auscultatory findings of pneumonia or consolidation (rales, rhonchi bronchial breath sounds, decreased breath sounds, wheezing, egophony)
– Dyspnea
– Increased work of breathing expressed as presence of retractions, nasal flaring, or grunting
– Hypoxemia (partial pressure of oxygen (PO2) <60mm Hg on room air) or oxygen saturation less than 90% on room air
– Tachypnea defined as follows:
> or = 50 breaths/minute for ages > or = 3 months to < or = 12 months
> or = 40 breaths/minute for ages >12 months to < or = 5 years
> or = 20 breaths/minute for ages >5 years of age
OR
apnea in infants <12 months of age
3 - Have a diagnosis of NP ,VAP, or severe CAP defined by the disease-specific criteria
specified below:
Nosocomial Pneumonia:
Subjects with NP must not be intubated or mechanically ventilated and must be hospitalized or reside in a chronic care facility for a minimum of
48 hours before being diagnosed with pneumonia.
Ventilator-associated pneumonia:
Subjects with VAP must be intubated and mechanically ventilated for > or = 48 hours before being diagnosed with pneumonia.
Severe community-acquired pneumonia:
Subjects with severe CAP must have pneumonia that is neither NP or VAP and must have at least ONE of the following risk factors for more severe disease or infection with a less susceptible pathogen:
– a mild to moderately immunocompromised condition including but not limited to diabetes or other metabolic disorder associated with immunosuppression, asplenia, sickle cell disease, mild to moderate neutropenia (ANC of 500 – 1500 cells/mm3), HIV infection not requiring Pneumocystis jirovicei prophylaxis, antibody deficiency syndromes not requiring chronic immunoglobulin replacement therapy, T-cell deficiencies not requiring prophylactic antibiotics or other chronic therapy for the immunodeficiency, phagocytic disorders, and receipt of non-inhaled corticosteroid therapy equivalent to <1 mg/kg of prednisone daily for 14 or more days during the 30 days before randomization,
– a documented tracheoesophageal

Exclusion Criteria

1 - Have a history of hypersensitivity reactions to carbapenems, cephalosporins, penicillins, or other ß-lactam antibiotics. Note: Subjects with a history of mild non-urticarial skin rash temporally related to but considered not associated with the previous use of ß-lactam antibiotics are permitted to enroll in the study. For such subjects, there must be a description of the rash and documentation by the investigator that upon review of the history it is his/her opinion that the rash was unlikely due to any of the above-mentioned classes of drugs for the subject to qualify for inclusion in the study.
2 - Concomitant infection including but not limited to suspected or confirmed meningitis, or other CNS infection, requiring systemic antibiotic or antifungal therapy at the time of randomization. (Clarification: possible bacteremia with a presumed respiratory pathogen is acceptable).
3 - Have received more than 24 hours of systemic antibacterial therapy in the 48 hours before the start of the infusion of the first dose of IV study drug therapy.
4 - Known presence at baseline of Stenotrophomonas maltophilia or Burkholderia cepacia pulmonary infection
5 - Known at the time of randomization to have mono-microbial pneumonia caused by a single pathogen that is nonsusceptible to doripenem or cefepime, including but not limited to MRSA or atypical bacteria.
6 - Have acute respiratory distress syndrome (defined by either diffuse bilateral radiographic infiltrates and/or a PaO2 to fraction of inspired oxygen (FiO2) ratio of <200)
7 - Acute or chronic renal insufficiency with a baseline CLCR <60 mL/minute or requires dialysis therapy for any reason.
8 - Are profoundly immunodeficient and require prophylactic antimicrobial therapy to
prevent infection with Pneumocystis jirovicei, Toxoplasma gondii, or herpes viruses,
and/or required chronic or intermittent immunoglobulin replacement therapy.

Study & Design

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