E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Late pneumonia in patients with ventilator breathing |
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E.1.1.1 | Medical condition in easily understood language |
Late pneumonia in patients who needs ventilator mechanical support for breathing |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052596 |
E.1.2 | Term | Nosocomial pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 demonstrate that colistin IV is not inferior to meropenem as empirical treatment of VAP, taking into account as an end point of primary efficacy: 28-day mortality. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that colistin is not inferior to meropenem as empiric treatment of VAP with respect to efficacy: clinical healing for intention to treat in clinically evaluable patients. To compare the microbiological efficacy of empirical treatment with colistin versus meropenem in VAP. To compare the security of the empirical treatment with colistin versus meropenem in VAP, including resistance development. To describe the pharmacokinetics of colistine in patients affected by VAP |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ? 18 years 2. At least 96h of mechanical ventilation 3. Suspicion of VAP defined for the following clinical and radiological criteria:
Clinical criteria of VAP, patients should have at least one of the following present at enrolment: - Documented fever, defined as a core temperature greater than or equal to 38.3 degrees Celsius (101 degrees Fahrenheit) or hypothermia, defined as a core body temperature of less than 35 degrees Celsius (95.2 degrees Fahrenheit). - An elevated total peripheral white blood cell (WBC) count (WBC greater than 10,000/mm); or greater than 15 percent immature neutrophils (bands), regardless of total peripheral WBC count; or leukopenia with total WBC less than 4,500/mm. - New onset of expectorated or suctioned respiratory secretions characterized by purulent appearance indicative of bacterial pneumonia
In addition, patients should have at least one of the following present at enrolment: - Auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation (e.g., dullness on percussion, bronchial breath sounds, or egophony) - Acute changes in arterial blood gases, or worsening PaO2/FiO2.
Radiological criteria of VAP: new or progressive pulmonar infiltrate in the thorax radiography which suggests pneumonia and with no other probable cause.
4. Modified Clinical Pulmonary Infection Score (CPIS) > 4 5. Respiratory secretion sample obtained from the respiratory tract by means of bronchoscope with broncoalveolar washing (BAL) or endotracheal aspirates, both quantitatively processed obtained in the 24 h. previous to the beginning of antimicrobial treatment of the study. 6. The women of childbearing age (not surgically sterilized and in the period between menarche and 1 year after the menopause) must have a negative test of pregnancy in urine at the time of recruitment. 7. The patient or his/her legal representative must sign a document of informed consent approved by the Ethics Review Committee. |
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E.4 | Principal exclusion criteria |
Hypersensitivity to any of the three antimicrobials of the study (colistin/ meropenem/levofloxacin). Renal insufficiency in substitute treatment. Corporal weight <40 kg or >150 kg. Patients currently included in another clinical trial. Refractory shock or another disease that, according to the researcher, presents a life expectancy inferior to 48 hours, after recruitment. Patients with known or suspected CABP or viral pneumonia Patients with acute exacerbation of chronic bronchitis without evidence of pneumonia Patients with tracheobronchitis Patients with primary lung cancer or another malignancy metastatic to the lungs Patients with cystic fibrosis, bronchiectasis, HIV/AIDS, known or suspected Pneumocystis jiroveci pneumonia, or known or suspected active tuberculosis. Immunocompromised patients; haematologic neoplasia, solid organ trasplant or congenital or acquired diseases that cause significant immunodeficiency (examples: common variable immunodeficiency, HIV infection with CD4 less than 200mm3, etc), Patients with neutropenia <500PMN/mm3 Isolation of BGN resistant to colistin or meropenem by systematic surveillance cultures in the 7 days previous to diagnosis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Evaluation of clinical cure in the clinically evaluable population. - Evaluation of microbiological cure in the microbiologically evaluable population. - Evaluation of cure, failure or indetermined at the end of the treatment. - Evaluation of cure, failure or relapse at the end of follow-up. - Safety evaluation in all the patients who received at least one antibiotic dose during the 28 days of follow-up. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 28 days of follow-up |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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End of the trial, last vist of last patient included |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |