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Combination lock01 - Impact of aminoglycosides-based antibiotics combination and protective isolation on outcomes in critically-ill neutropenic patients with sepsis:A randomized 2 by 2 factorial design randomized pragmatic trial

Phase 3
Recruiting
Conditions
Adult patients admitted to intensive care
Registration Number
2024-514042-36-00
Lead Sponsor
Assistance Publique Hopitaux De Paris
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruiting
Sex
Not specified
Target Recruitment
340
Inclusion Criteria

Age ≥ 18 years

Admitted in one of the participating ICU

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

Exclusion Criteria

Pregnancy and breastfeeding

Myasthenia gravis

Concomitant administration of intravenous Polymyxin - Delay between onset of sepsis and inclusion>24 hours

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

Contraindication to aminoglycosides as mentioned in SpC section 4.3

Hypersensitivity to amikacin, to other antibiotics from the aminoglycoside family, or to any excipient from the amikacin used

Patients with documented allergy to aminoglycosides

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Day-90 mortality

Day-90 mortality

Secondary Outcome Measures
NameTimeMethod
Day-28 and hospital mortality

Day-28 and hospital mortality

Incidence and severity of AKI according to KDIGO definition

Incidence and severity of AKI according to KDIGO definition

Major Adverse Kidney Events at day-28 and day 90 (composite of death, new renal replacement therapy, or persistent renal dysfunction)

Major Adverse Kidney Events at day-28 and day 90 (composite of death, new renal replacement therapy, or persistent renal dysfunction)

Incidence of clinically apparent loss of hearing at end of ICU stay and day 90

Incidence of clinically apparent loss of hearing at end of ICU stay and day 90

Rate of adherence to adequate hand hygiene as assessed by external observer

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 selected serious adverse events including unexpected cardiac arrest

Incidence density of new bacterial, viral or fungal episode

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

Number of days free from organ support therapy (mechanical ventilation, vasopressors or RRT) at day 28

Rate of clinical cure

Rate of clinical cure

Frequency of initial antibiotic therapy inadequate as regard to microbiological documentation.

Frequency of initial antibiotic therapy inadequate as regard to microbiological documentation.

Number of day free of antibiotic therapy at day-28

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

Duration of aminoglycoside therapy, rate of aminoglycoside overdosage according to residual concentration and overuse when compared to experts recommendations

Trial Locations

Locations (7)

Assistance Publique Hopitaux De Paris

🇫🇷

Paris, France

Centre Hospitalier Universitaire D'Angers

🇫🇷

Angers, France

Hospices Civils De Lyon

🇫🇷

Lyon Cedex 03, France

University Hospital Of Clermont-Ferrand

🇫🇷

Clermont Ferrand Cedex 1, France

Centre Hospitalier Universitaire De Saint Etienne

🇫🇷

Saint Priest En Jarez, France

Centre Hospitalier De Versailles

🇫🇷

Le Chesnay Rocquencourt, France

Centre Hospitalier Universitaire De Lille

🇫🇷

Lille Cedex, France

Assistance Publique Hopitaux De Paris
🇫🇷Paris, France
Frédéric PENE
Site contact
0158412517
frederic.pene@aphp.fr
Thomas URBINA
Site contact
0149282000
thomas.urbina@aphp.fr
Maxens DECAVELLE
Site contact
0184827939
maxens.decavele@aphp.fr
Michael DARMON
Site contact
0142499222
michael.darmon@aphp.fr

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