E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nosocomial and Ventilator-Associated Pneumonia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065153 |
E.1.2 | Term | Ventilator associated pneumonia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052596 |
E.1.2 | Term | Nosocomial pneumonia |
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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 evaluate clinical response and safety of a new carbapenem in the treatment of subjects with nosocomial pneumonia (NP) or ventilator-associated pneumonia (VAP) in hospitals where Pseudomonas aeruginosa may be a prevalent pathogen. |
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E.2.2 | Secondary objectives of the trial |
Other objectives are to gain experience with doripenem as part of a combination antibacterial regimen and to collect medical resource utilization data. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Microbiological samples (respiratory secretions) suitable for culture and microscopy (e.g., obtained via BAL, PSB, mini-BAL, deep suction via endotracheal tube [including through a tracheostomy tube], nasotracheal aspiration specimen or suitable expectorated sputum). Note: Suitable specimens from expectorated samples are defined as having </= to 10 squamous epithelial cells and >/= 25 leukocytes per low power field (10 x objective). If the initial collection of respiratory secretions is obtained via bronchoscope (BAL, PSB) or via mini-BAL (done using a prepackaged, commercially available telescoping catheter, passed through the endotracheal tube), then a sample of respiratory secretions should be obtained simultaneously via deep suctioning through the endotracheal tube or tracheostomy tube. This will allow for a more accurate comparison between a sample obtained at study entry and the required subsequent respiratory samples.
2. CPIS >/= 6 at baseline in subjects with VAP.
3. APACHE II score >/= 8 and </= 35.
4. Subjects suffering from NP or VAP defined as follows: Nosocomial Pneumonia (Subjects must have a, b, and c) a) Clinical signs and symptoms of de novo pneumonia after >/= 5 days of hospitalization or residence in a chronic care facility. Clinical signs and 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 or respiratory secretions already present. • Tachypnea (respiratory rate >/= 20/minute), particularly if progressive in nature. • De novo hypoxemia with a PO2 </= 60 mmHg while subject is breathing on room air, as determined by arterial blood gas. b) New radiographic infiltrates (not related to another disease process). c) Fever or leukocytosis/leukopenia consistent with a diagnosis of pneumonia with AT LEAST 1 of the following at evaluation: • Leukocytosis defined as AT LEAST 1 of the following: Hospital baseline WBC was normal, but subsequently increased to >/=10,500. Exception: If hospital baseline WBC was significantly above or below 10,500, an increase of at least 25% from the baseline WBC will also constitute leukocytosis. >/= 10% immature neutrophils (bands). • Leukopenia defined as </=4,500. • Fever or documentation of a history of fever ([in the absence of antipyretics], increase in core temperature of >1°C OR a rectal or oral temperature >38°C, a tympanic temperature >38.4°C OR hypothermia, defined as a rectal/core body temperature of <35°C) within the past 24 hours. |
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E.4 | Principal exclusion criteria |
1. Known or suspected severe renal impairment, (i.e., a calculated creatinine clearance [CrCl] <10 mL/minute) or oliguria (less than 20 mL urine output per hour over 24 hours unresponsive to fluid challenge), or requiring peritoneal dialysis, hemodialysis, or hemofiltration.
2. Known or suspected hepatic dysfunction based on history or previous laboratory values during hospitalization (total bilirubin, or alanine aminotransferase [ALT], or aspartate aminotransferase [AST] >/= 3 times upper limit of the normal range [ULN]). Contact medical monitor if upper limit of normal is >/= 3 times and subject does not have any underlying hepatic disease or disorder.
3. Subjects who have a history of or who are at high risk for seizure disorder or stroke who are not on preventative medication or therapy.
4. Known to be HIV-positive with CD4 counts of </= 0.2x10(to the power 9) /L (</=200 cells/mm3) observed within the last 6 months prior to study entry. (Subjects with HIV and CD4 counts of >0.2x10(to the power 9) /L [>200 cells/mm3] may be included.)
5. Presence of myelosuppression or neutropenia (ANC <0.5 x 10(to the power 9) /L [<500 PMNs/mm3], unless recovering from chemotherapy and expected to exceed 500 PMNs/mm3 in 24 hours), severe anemia (hemoglobin <6.5 g/dL, not due to acute blood loss) or severe thrombocytopenia (<49.9 x 10(to the power 9) /L) based on CBC results. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical response (clinical cure, failure, unable to evaluate), as the primary endpoint, will be assessed at the TOC assessment. Pathogen burden will be tracked and correlated with clinical response. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |