Clinical trial NCT03961503: Retrospective Analysis of Nephrotoxicity During Daptomycin Versus Vancomycin Treatments in High Risk Patients
Official title: Acute Kidney Injury During Daptomycin Versus Vancomycin Treatment in Cardiovascular Critically Ill Patients: a Propensity Score Matched Analysis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infective Endocarditis
Infection Related to Ventricular Assist Device
Infection Related to Vascular Prothesis
Surgical Site Infection
Mediastinitis
Keywords: Vancomycin
Daptomycin
Acute Kidney Injury
Nephrotoxicity
Infective Endocarditis
Foreign Body Associated Infection
Cardiovascular surgery
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2019-05-23
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient admitted in Intensive Care Unit before and/or after cardiovascular surgery with at least one organ failure

Brief summary: Acute kidney injury (AKI) is a frequent complication that occurs in 15 to 25% of patients after vascular surgery, and up to 40% of patients after cardiac surgery. AKI compromises seriously short and long-term prognosis of critically ill patients. Several AKI risk factors have been identified including a chronic pathology of the patient such as kidney failure or diabetes, acute kidney injury related to hemodynamic disorders during surgery, including cardiopulmonary bypass, or sepsis, and the use of nephrotoxic agents such as some antibiotics, colloids or iodine contrast agents. Avoiding nephrotoxic agents is therefore strongly recommended in ICU patients, to reduce the incidence of AKI, or to reduce its severity.

The aim of this cohort study was to assess whether the use of daptomycin, was associated to a lower incidence of AKI than vancomycin in cardiovascular ICU patients, with similar efficacy.

This is a retrospective observational study with a propensity score adjustment to reduce the bias of selection for a comparative analysis between two antibacterial treatments used in routine care.

Since treatments were not randomized, the investigators used the propensity score method for primary endpoint analysis. For this, the investigators included the covariates potentially related to treatment and outcome in a multivariate logistic model explaining the choice of treatment. This propensity score was used in the second model as an adjustment covariate included in the multivariate analysis to determine factors independently associated with the primary endpoint (AKI within 7 days).

The main hypothesis is the first line antibiotic treatment with daptomycin leads to less nephrotoxicity than vancomycin in a population known at high risk for AKI and with at least a similar efficacy on clinical success rate.


Eligibility criteria: Inclusion criteria:

* Patient older than 18 years
* Admitted in ICU from January 2010 to December 2012
* Suspected or proven cardiac, vascular or profound surgical site infection with Gram-positive cocci (GPC) methicillin-resistant (MR) strains (including probabilistic treatment for patients with acquisition of MR risk factors)
* Treatment duration greater than or equal to 48 hours (at least 2 doses of daptomycin administered or 2 days of vancomycin infusion)
* Antibiotic treatment started in peri-operative (from 48 hours before the onset of surgery) or in postoperative period (during ICU stay)

Exclusion criteria:

* Prophylaxis indication of antibiotics
* Kidney disease on chronic dialysis
* Acute onset of RRT before initiation of DAP or VAN treatment
* Staphylococcus pneumonia

Primary outcomes:
measure: Incidence of Acute Kidney Injury (AKI)
timeFrame: 7 days after the treatment initiation
Secondary outcomes:
measure: Incidence of Acute Kidney Injury (AKI)
timeFrame: 14 days after the treatment initiation
measure: Maximal decrease of glomerular filtration rate (GFR)
timeFrame: Through study treatment completion, an average of 2 weeks
measure: Incidence of severe renal failure
timeFrame: Through study treatment completion, an average of 2 weeks
measure: Incidence of renal replacement therapy (RRT)
timeFrame: Through study treatment completion, an average of 2 weeks
measure: Duration of RRT
timeFrame: Through study completion limited to ICU stay, an average of 2 weeks
measure: Incidence of clinical treatment failure
timeFrame: 15 days after the end of treatment
measure: Incidence of premature discontinuation of treatment
timeFrame: Through study treatment completion, an average of 2 weeks
measure: Mortality
timeFrame: 28 days after treatment initiation
measure: Mortality
timeFrame: 6 months (180 days) after treatment initiation
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Uh Montpellier
Study officials:
affiliation: University Hospital, Montpellier
name: Philippe Gaudard, MD
role: PRINCIPAL_INVESTIGATOR
References: