Clinical trial NCT01932814: Acute Kidney Injury in Septic Critically Ill Patients : Are Aminoglycosides Really Harmful?
Official title: Retrospective Analysis of Aminoglycoside-associated Acute Renal Injury in Septic Critically Ill Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Kidney Injury
Severe Sepsis
Keywords: Aminoglycosides
Acute kidney injury
Severe sepsis
Critically ill patient
Lead sponsor: Université Victor Segalen Bordeaux 2
Sponsor class: OTHER
First posted: 2013-08-30
Enrollment: 317
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: critically ill septic patients

Brief summary: The purpose of the present study is to determine whether administration of aminoglycosides in septic critically ill patient is a risk factor for acute kidney injury

Detailed description: Severe sepsis and septic shock despite recent advances in surviving sepsis campaign remain encumbered by a high mortality rate close to 30%. One cornerstone of the management of these patients remains the early and appropriate antibiotic administration, , which must be also active at the site of infection. Aminoglycosides are often administered in combination with beta lactams in this context . According to the progress in pharmacokinetic management achieved over the past decade, their safety and efficiency tended to increase but many uncertainties remain. The purpose of the present study is to determine whether administration of aminoglycosides in septic critically ill patient is a risk factor for acute kidney injury.

Study design: This is an open retrospective monocentric cohort study including septic critically ill patients from november 2008 to january 2010. To determine the incidence and the specific risk of nephrotoxicity of aminoglycosides, only hospitalized patients without initial acute kidney injury or with rapidly improving kidney function during the three first days will be included.Primary outcome will be the occurrence of acute kidney injury assessed with the RIFLE classification (Risk, Injury, Failure, Loss, and End-stage kidney disease) from day 4 to day 15. Patients receiving aminoglycosides will be compared with a control group, i.e. not receiving them. We estimated hazard ratios (HR) and 95% confidence intervals (CI) with adjusted and propensity score (PS)-matched Cox-proportional hazards models.

Eligibility criteria: Inclusion Criteria:

* Age 18 and older
* Admission to ICU with severe sepsis
* Hospitalized and without acute kidney injury or with kidney function improved on the third day were included
* Information provided to the patient or proxy

Exclusion Criteria:

* Renal replacement therapy before day 3
* Patients with renal insufficiency J1 (Day 1 creatinine clearance \<56.25 ml/mn/1, 73m2) but severely altered between Day 1 and Day 3 (creatinine clearance Day 1/ Day 3\> 1 + Day 3 creatinine clearance \<37.5 ml/mn/1, 73m2 ) without renal replacement therapy still necessary before J3
* Prolonged aminoglycosides therapy

Primary outcomes:
measure: The incidence of acute renal injury associated with treatment with aminoglycoside in critically ill septic patients
timeFrame: between day 4 and day 15
Secondary outcomes:
measure: Risk factors of acute kidney injury
timeFrame: between day 1and day 3
Other outcomes:
measure: Risk factors for ICU mortality
timeFrame: between day 4 and day 15
measure: Pharmacokinetics parameters of aminoglycosides
timeFrame: between day 1 to day 6
Locations:
city: Bordeaux
country: France
facility: Service de Réanimation médicale, Hôpital Pellegrin
state: Aquitaine
Study officials:
References:
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citation: Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999 Feb;115(2):462-74. doi: 10.1378/chest.115.2.462.
citation: Kumar A, Safdar N, Kethireddy S, Chateau D. A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: a meta-analytic/meta-regression study. Crit Care Med. 2010 Aug;38(8):1651-64. doi: 10.1097/CCM.0b013e3181e96b91.