E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient with mechanical ventilation through an endotracheal tube |
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E.1.1.1 | Medical condition in easily understood language |
Patient with mechanical ventilation through an endotracheal tube |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065153 |
E.1.2 | Term | Ventilator associated pneumonia |
E.1.2 | System Organ Class | 100000004862 |
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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 prove that after the third day of invasive mechanical ventilation a three-day course of inhaled amikacin reduces the incidence of subsequent VAP |
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E.2.2 | Secondary objectives of the trial |
To prove that a three-day course of inhaled amikacin reduces the incidence of subsequent VAP in the subgroup of patients with tracheobronchial bacterial colonization and with tracheobronchitis at randomization, subsequent VAP due to Gram negative bacteria sensitive to amikacin,clinical signs of tracheobronchial and lung infection, reduces the subsequent use of systemic antibiotics, the length of stay in the intensive care unit and in the hospital and intensive care unit, hospital, day28 and day90 mortality, speeds up weaning from mechanical ventilation and is not associated with an increased incidence of acute kidney injury. To assess the impact on the incidence of antibiotic-resistant bacteria nosocomial infection and rectal carriage of antibiotic resistant bacteria and the respiratory and digestive microbiota composition over a subsample of included patients. To assess pharmacokinetics of inhaled amikacin in a large multicenter sample over a subsample of included patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥ 18 years the day of inclusion - Mechanical ventilation through an endotracheal tube for more than three consecutive days (72h) - Written informed consent of the patient or a proxy - Patients covered by or having the rights to French social security
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E.4 | Principal exclusion criteria |
- Suspicion or confirmed VAP - Clinical indication for systemic aminoglycoside therapy - Stage 3 KDIGO classification acute kidney injury excepted in patients undergoing renal replacement therapy - Patient scheduled for extubation within the next 24h - Patient ventilated more than 4 days before inclusion (96h) - Patient ventilated through a tracheostomy - Patients allergic to aminoglycosides - Myasthenia gravis - Pregnant or lactating patients - Patients undergoing guardianship or trusteeship - Patients previously included in this study
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of a first VAP episode from randomization to day 28:
diagnosis will be standardized : two criteria among hyperleukocytosis/leukopenia, fever, purulent secretion with a new chest X-ray infiltrate and significant bacterial growth in a pulmonary sample. Outcome will be adjudicated by a blinded committee at study end.
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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) |
From randomization to day 28:
- Incidence of a first VAP episode in the subgroups of patients with tracheobronchial colonization or tracheobronchitis at randomization Incidence of VAP due to Gram negative amikacin sensitive bacteria - Clinical pulmonary infection score evolution - Ventilator associated events incidence - Number of systemic antibiotics administered per day - Number of days with at least one administration of a systemic antibiotic - Incidence of antibiotic resistant bacteria isolated on clinical and hygiene samples - Incidence of acute kidney injury
- Days spent on mechanical ventilation from randomization to day 90 - Days from randomization to the first successful spontaneous breathing trial - Days spent in the intensive care unit and in the hospital after randomization - Intensive care unit, hospital, day-28 and day-90 mortality - Incidence of bacteria producing extended spectrum beta-lactamase or high level derepressed celphalosporinase, of vancomycin resistant Enterococcus Sp. on rectal samples at discharge compared to randomization - Relative bacterial species composition of respiratory and digestive microbiota - Sputum and serum amikacin population pharmacokinetics - Respiratory mechanics before and after aerosol
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
randomization to day 28, at the end of ICU-stay, day 28, day 90 |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 22 |
E.8.5 | The trial involves multiple Member States | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |