E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
neutropenic patients with sepsis |
patients neutropéniques admis en réanimation avec un sepsis |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 the impact on day-90 mortality of two strategies, separately, using a 2x2 factorial design RCT: • Intervention 1 - routine association of aminoglycoside to initial antibiotic therapy when compared to standard of care • Intervention 2 - lack of routine use of protective isolation when compared to standard of care
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Évaluer l'impact sur la mortalité à J90 de deux stratégies, séparément, en utilisant un plan factoriel 2x2 : - Intervention 1 - association systématique d'aminoglycosides à l'antibiothérapie initiale par rapport à la norme de soins - Intervention 2 - Absence de recours systématique à l'isolement protecteur par rapport à la norme de soins |
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E.2.2 | Secondary objectives of the trial |
To evaluate the impact of the studied interventions, on - Day-28 and hospital outcome - Incidence, severity and duration of AKI - Rate of adherence of hand hygiene - Rate of selected adverse events - Rate of nosocomial bacterial, viral and fungal infection episodes - Organ support during ICU stay and organ support duration - Failure of initial antibiotic therapy - Antibiotic duration - Rate of aminoglycosides overdosage and overuse
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Evaluer l’impact des stratégies testées : - Mortalité à J28 et à l’hôpital - Incidence, sévérité et durée de l’insuffisance rénale aiguë - Adhésion à l’hygiène des mains - Taux d’évènement indésirable - Taux d’infection nosocomiale bactérienne, virale et fongique - Suppléances vitales et durée de ces dernières - Echec de l’antibiothérapie - Durée d’antibiothérapie - Quantité d’aminosides reçues et surdosages
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥ 18 years - Sepsis or septic shock as defined by SEPSIS3 definition - Underlying tumor, allogeneic stem cell transplantation or hematological malignancy - Neutropenia (defined by either absolute neutrophil count <500/mm3 or leucocytes <1000/mm3) related to an underlying malignancy or its treatment - Informed or deferred consent
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- Age ≥ 18 ans Admission en réanimation - Sepsis ou choc septique selon la définition SEPSIS3 - Tumeur solide, greffe de moelle ou maladie hématologique tumorale - Neutropénie (PNN <500/mm3 ou leucocytes <1000/mm3) en lien avec le traitement de l’hémopathie - Consentement du patient, du proche ou inclusion selon un critère d’urgence
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E.4 | Principal exclusion criteria |
- Pregnancy and breastfeeding - Moribund patients (death expected within 48 hours by attending physician) - Previous participation to this study - No affiliation to social security - Patients under legal protection according to French Law - Patient having received more than 1 injection of aminoglycosides in the 3 days preceding ICU admission - Hypersensitivity to amikacin, to other antibiotics from the aminoglycoside family, or to any excipient from the amikacin used. - Patients with documented allergy to aminoglycosides - Delay between admission for a new sepsis and inclusion>24 hours or (in patients previously admitted in the ICU for another reason) delay between new sepsis in study inclusion >24h
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- Grossesse ou allaitement - Survie attendue <48h - Participation antérieure à l’étude - Absence d’affiliation à un régime de sécurité social - Patient majeur protégé ou privé de liberté - Patient ayant reçu plus d'une injection d'aminoglycosides dans les 3 jours précédant - Hypersensibilité aux aminosides ou à l'un des excipients de l'amikacine. - Délai entre l'admission pour sepsis et l'inclusion> 24 heures ou (chez les patients admis en réanimation pour une autre raison), délai entre le sepsis et l’inclusion > 24h
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E.5 End points |
E.5.1 | Primary end point(s) |
Day-90 mortality
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Mortalité à J90 |
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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) |
- Day-28 and hospital mortality - Incidence and severity of AKI. - Major Adverse Kidney Events at day-28 and day 90. - Rate of adherence to adequate hand hygiene as assessed by external observer. - Incidence density of selected serious adverse events including unexpected cardiac arrest. - Incidence density of new bacterial, viral or fungal episode. - Number of days free from organ support therapy (mechanical ventilation, vasopressors or RRT) at day 28 - Rate of clinical cure - Frequency of initial antibiotic therapy inadequate as regard to microbiological documentation. - Number of day free of antibiotic therapy at day-28 - Duration of aminoglycoside therapy, rate of aminoglycoside overdosage according to residual concentration and overuse when compared to experts recommendations
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- Mortalité à J28 et en réanimation - Incidence et sévérité de l’IRA. - Major Adverse Kidney Events à J28 et J90. - Taux d’hygiène des mains répondant aux crtéres de bonne qualité tel qu’evalué par un observateur extérieur. - Densité d’incidence d’évènement indésirable sévère dont l’arrêt cardiaque non anticipé. - Densité d’incidence des nouveaux épisodes d’infections bactérienne, viral et fongique. - Nombre de jour vivant libre de suppléance vitale (ventilation mécanique, amines et épuration extra-rénale). - Taux de guérison de l’infection motivant l’admission. - Taux d’antibiothérapie inadéquate. - Nombre de jours vivant sans antibiotique à J28 - Durée du traitement par aminoside, taux de surdosage définit selon le taux résiduel et taux d’utilisation considérée comme excessive lorsque comparé aux recommandations.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | No |
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 | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
• Intervention 1 – Absence d’adjonction systématique d’aminoside • Intervention 2 – Isolement prote |
• Intervention 1 - Antibiotic therapy without systematic adjunction of aminoglycosides • Interventi |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 14 |
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 | Information not present in EudraCT |
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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Last follow-up of the last patient |
Dernier suivi du dernier patient |
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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 | 12 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |