Randomized, double-blind, multicenter study to evaluate efficacy and safety of intravenous iclaprim versus vancomycin in the treatment of hospital-acquired, ventilator-associated, or health-care-associated pneumonia suspected or confirmed to be due to Gram-positive pathogens

• Conditions: Hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or health-care-associated pneumonia (HCAP) suspected or confirmed to be due to Gram-positive pathogens.; MedDRA version: 9.1Level: LLTClassification code 10035664Term: Pneumonia

• Registration Number: EUCTR2007-003109-28-LT
• Lead Sponsor: Arpida AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-08-01
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

Patients will be considered for further screening procedures in this study only if they meet both of the following criteria:
1. Suspected or confirmed acute bacterial pneumonia due to Gram-positive pathogens in one of the following subgroups:
- hospital-acquired pneumonia (HAP), i.e., pneumonia that occurs 48 hours or more after admission, which was not incubating at the time of admission; or
- ventilator-associated pneumonia (VAP), i.e., pneumonia that arises more than 48 hours after endotracheal intubation; or
- healthcare-associated pneumonia (HCAP), i.e., pneumonia diagnosed within 48 hours of hospital admission, in a patient who fulfills at least one of the following criteria:
- hospitalization for at least two days within 90 days of the current infection,
- residence in a nursing home or long-term care facility,
- recipient of intravenous antibiotic therapy, chemotherapy, or wound care within 30 days of the current infection
2. Venous access available for intravenous dosing.
3. At least 2 of the following signs and symptoms typical of acute bacterial pneumonia:
- cough,
- new onset of purulent sputum production or a change (worsening) in character of the sputum,
- auscultatory findings on pulmonary examination of rales and/or pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony),
- dyspnea, tachypnea, or hypoxemia with a partial pressure oxygen (PO2) <60 mmHg, particularly if any or all of these are progressive in nature,
- organism consistent with a respiratory pathogen isolated from cultures of respiratory tract, sputum or blood sample; and
- at least 2 of the following signs and symptoms:
- fever (oral temperature >38oC/100.4oF, tympanic temperature >38.5oC/101.2oF, rectal/core temperature >39.0oC/102.2oF) or hypothermia (rectal/core temperature <35oC/95.2oF),
- For non-intubated patients only: respiratory rate >30 breaths per minute,
- pulse rate =120 beats per minute (bpm),
- altered mental status,
- leucocytosis with white blood cell (WBC) count >10,000/mm3,
- leucopenia with WBC count <4500/mm3,
- >15% immature neutrophils (bands), regardless of total peripheral WBC count.
4. Pulmonary infiltration consistent with the diagnosis of pneumonia (new or progressive infiltrates, consolidation, or pleural effusion) documented by chest X ray within 48 hours prior to randomization, as interpreted by the radiologist or investigator. The infiltrate must be new, and not likely to be related to another clinical process or condition (for example, congestive heart failure or acute respiratory distress syndrome), as judged by the investigator.
5. Suitable respiratory specimen (sputum/endotracheal/nasotracheal specimen or specimen from invasive procedure) for culture, and Gram stain, with indication of Gram-positive pathogens. Average of at least 10 organisms per oil-immersion field in 10 fields (actual or calculated, at 100x magnification, i.e. low-power, 10 x objective).
For sputum samples, additionally fulfilling both of the following criteria:
- =10 squamous epithelial cells, and
- =25 leucocytes per low power field (100x) in 10 to 20 fields.
If one or both of the above two additional criteria are not met a specimen is still considered acceptable provided a justification is entered into the CRF.
If the baseline respiratory specimen is obtained by an invasive technique (bronchoscopic or non-bronchoscopic), it is acceptable to obtain the specimen within 24 hours after starting study drug.
6. CPIS >6

Exclusion Criteria

1. APACHE II score <8 or =25.
2. Pneumonia not requiring empiric or targeted treatment effective against Gram-positive pathogens.
3. Pulmonary infection due to Gram-positive organisms known to be resistant to either study medication prior to study entry.
4. No requirement for Gram-positive antibiotic coverage based on available culture and Gram stain results.
5. Previous systemic antimicrobial therapy, effective against Gram-positive pathogens, for more than 24 hours within 48 hours prior to enrollment.
Exceptions include:
a) The current pneumonia is caused by microbiologically-confirmed pathogens.
b) The current pneumonia is most likely caused by MRSA, as indicated by a rapid blood test, and the previously received antimicrobial therapy is known to be ineffective against MRSA or if effective against MRSA was given for less than 24 hours within the 48 hours prior to enrollment into the study.
6. Requirement for empiric treatment for suspected or confirmed concurrent Gram-negative bacterial infection with antibiotics other than aztreonam.
7. Concomitant morbidity of such severity that the patient is likely to die or present with severe medical conditions within 7 days of study entry.
Patients with stroke should not be enrolled within 5 days of the stroke onset.
Additionally, patients with stroke should not be enrolled if at least one or both of the following apply:
a) There is an increased risk of fatal brain edema as indicated by: history of hypertension of heart failure, major early CT hypodensity exceeding 50% of the MCA territory, and/or involvement of additional vascular territories.
b) There is indication for deterioration based on comparison of patient's neurological condition within 6 hours of planned study drug dosing and 2 days before, judged by applying NIH Stroke Scale (NIHSS) (see Appendix 11.4).
8. Known or suspected pulmonary conditions which are likely to preclude therapeutic response, such as:
- evidence of active tuberculosis or other mycobacterial infections,
- cystic fibrosis,
- bronchial obstruction,
- post-obstructive pneumonia other than chronic obstructive pulmonary disease (COPD),
- known or suspected Pneumocystis jiroveci (Pneumocystis carinii) infection,
- granulomatous disease,
- lung cancer or another malignancy metastatic to the lungs,
- acute respiratory distress syndrome (ARDS).
9. Presence of severe sepsis at the time of entry into the study defined as acute occurrence of non-pulmonary organ dysfunctions or acute worsening of chronic non-pulmonary organ dysfunction within the last 48 hours that is not attributable to an alternative process.
10. Empyema as confirmed by thoracentesis or clearly defined by computed tomography (CT) scan.
11. History of lung transplant or a recent history of bone marrow transplant in post-transplant hospital stay.
12. Known or suspected Legionella pneumophila pneumonia.
13. Documented or suspected meningitis, endocarditis, or osteomyelitis.
14. Known or suspected human immunodeficiency virus (HIV) with helper/inducer T lymphocyte (CD4+) count <200 cells/mm3.
15. Immunocompromised, defined as WBC count <1000 cells/mm3 or absolute neutrophil count (ANC) <500 cells/mm3.
16. Current hemodialysis.
17. Body mass index (BMI) <18 or >40 kg/m2.
18. Body weight <34 kg or >133 kg.
19. Any underlying condition or disease that would interfere with the completion of the study procedures or any other condition that in the opinion of the investigator, would confound or interfere with the e

Study & Design

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