A Phase II, prospective, randomized, double-blind, active-controlled, parallel group, multi-center 'proof of concept' trial in adult patients with community-acquired pneumonia requiring hospitalization without evidence of Legionella

• Conditions: Community-acquired pneumonia

• Registration Number: EUCTR2004-002798-21-HU
• Lead Sponsor: F.Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-05-18
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Patients will qualify to participate in this study if they meet all of the following:
1. Are male or female patients greater than or equal to 18 years of age that require hospitalization with community-acquired pneumonia or develops pneumonia within 48 hours of hospitalization for another condition.
2. Have fever defined as body temperature > 38.0°C (100.4°F) taken orally; or > 38.5°C (101.2°F) tympanically; OR have hypothermia, defined as rectal or core body
temperature < 36°C (96.8°F).
3. Have a new or increased cough productive of purulent sputum for culture and
susceptibility testing.
4. Have either pleuritic chest pain, dyspnea, or tachypnea.
5. Have auscultatory findings consistent with pneumonic consolidation or pneumopathic process consistent with the diagnosis of pneumonia.
6. Have chest x-ray confirmation of infiltrate or lobar consolidation.
7. Have obtained respiratory secretion specimen and two blood cultures prior to administration of IV study drug or non-study short acting third generation cephalosporine. (Respiratory
secretions may be obtained by any of the following means: deep expectoration either unassisted or in conjunction with hydration followed by chest physiotherapy and nebulization treatments, nasotracheal aspiration, bronchoscopy with endobronchial lavage or protected-brush sampling, transtracheal aspiration, percutaneous lung or pleural fluid aspiration).
8. Have a negative urine Legionella antigen test (Binax®).
9. If the patient is sexually active and is female of child bearing potential, or is a sexually active male who has a female partner of child bearing potential, then the patient agrees to use two forms of contraception, at least one of which is a barrier method, during the study period.
10. Have an elevated total peripheral white blood cell count (WBC) greater than or equal to 10,000/mm3, or 15 % immature neutrophils (bands), regardless of total peripheral white count, or leukopenia with total WBC < 4500/mm3.
11. Have signed an informed consent.
Are the trial subjects under 18?
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

Patients will be excluded if they meet any of the following:
1. Have a Pneumonia Severity Index <71 or >130.
2. Have presented with sustained shock, defined as systolic blood pressure < 90 mm Hg for > 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents to maintain blood pressure.
3. In the opinion of the investigator, history, physical examination and chest X-ray
findings are most consistent with an atypical pneumonia.
4. Require endotracheal intubation and ventilation, or in the opinion of the investigator, are expected to require it.
5. Are likely to be discharged in less than 3 days.
6. Developed pneumonia after more than 48 hours of admission to hospital.
7. Have been a resident in a nursing home or extended care facility within 60 days prior to randomization.
8. Require hemodialysis, peritoneal dialysis, plasmapheresis or hemoperfusion.
9. Have a known bronchial obstruction or a history of post-obstructive pneumonia.
10. Have known or suspected lung abscess, empyema, or evidence of a pleural effusion estimated to be > 500 mL.
11. Have primary lung cancer or another malignancy metastatic to the lungs.
12. Have signs of meningitis such as nuchal rigidity, papilledema or other findings of
meningitis. (Note: The penetration of RO4908463 into the cerebral spinal fluid (CSF) has not yet been determined.)
13. Have known or suspected cystic fibrosis or suspected active tuberculosis.
14. Have known or suspected concomitant bacterial infection requiring antibiotic
treatment.
15. Require chronic immunosuppressive therapy or have an anticipated need for
immunosuppressive therapy for > 1 month from baseline (including > 10 mg/day of
systemic prednisone or equivalent).
16. Have neutropenia (ANC < 1000/mm3) or platelet count < 50,000/mm3.
17. Have any form of epilepsy or history of seizures.
18. Have been alcohol or drug dependent within the past six months.
19. Have hypersensitivity to beta-lactam antibiotics.
20. Have had more than one dose of a short acting, 3rd generation cephalosporin (e.g., cefotaxime) or any dose of a quinolone, macrolide or ketolide within 24 hours of
being randomized for participation in the study.
21. Have a history of cerebrovascular accident, transient ischemic attack(s), brain
metastases, space occupying lesion in the CNS or systemic malignancy within past
year and/or are currently receiving adjuvant chemotherapy.
22. Are receiving or likely to receive coumarin or probenecid therapy during the study.
23. Have a creatinine clearance, using the Cockcroft-Gault equation, of = 60 mL/min.
24. Have significant proteinuria (e.g. 4+ or > 1.0% or > 10g/L on urinalysis).
25. Have evidence of a liver dysfunction manifested by: ALT or AST = 4X ULN or total
bilirubin > 1.5X ULN.
26. Have a history of hemolytic anemia.
27. Have artificial heart valves or vascular prostheses.
28. Have known HIV infection or AIDS with a CD4 count < 250 cells/mm3 and are
taking antiretroviral therapy or in the opinion of the investigator should begin
antiretroviral treatments or have undiagnosed HIV infection but have clinical findings
highly suggestive of HIV/AIDS.
29. Are unlikely to comply with the dosing regimen, scheduled assessments, or complete the study for any other reason.
30. Have previously been randomized into this study or are ancillary personnel involved with this study.
31. Are pregnant or nursing.
32. Have any concomitant condition which could preclude evaluation of respons

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the safety, tolerance and efficacy of parenteral RO4908463 to ceftriaxone in patients with community-acquired pneumonia requiring hospitalization without evidence of Legionella.;Secondary Objective: To obtain in vitro susceptibility data on RO4908463 on the pathogenic organisms isolated from patients participating in the study.<br> <br>To evaluate the pharmacokinetics of RO4908463 in the patient population including the influence of covariates.<br><br>To explore the relationship of drug exposure (time above minimum inhibitory<br>concentration (MIC)) to clinical cure rates in the bacteriologic evaluable population.;Primary end point(s): The primary efficacy variable is the clinical cure rate at the end of study evaluation visit.