Retrospective Analysis of Nephrotoxicity During Daptomycin Versus Vancomycin Treatments in High Risk Patients

Surgical Site Infection Clinical Trial

— DVN  

Official title:

Acute Kidney Injury During Daptomycin Versus Vancomycin Treatment in Cardiovascular Critically Ill Patients: a Propensity Score Matched Analysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03961503
• Other study ID #: Q-2015-05-03
• Status: Completed
• Start date: January 1, 2016
• Est. completion date: January 30, 2016

Study information

• Verified date: May 2019
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: January 30, 2016
• Est. primary completion date: January 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Communicable Diseases
• Endocarditis
• Endocarditis, Bacterial
• Infection
• Infection Related to Vascular Prothesis
• Infection Related to Ventricular Assist Device
• Infective Endocarditis
• Mediastinitis
• Surgical Site Infection
• Surgical Wound Infection

Intervention

Drug:
• Daptomycin (DAP) treatment
Group DAP : Daptomycin was administered at a dose of 8 mg/kg in thirty-minutes intravenous infusion every 24 hours in patients without severe impairment of kidney function or every 48 hours in case of GFR below 30 ml/min/m2. The creatine-kinase (CK) level was measured before the initiation of DAP and at least once a week to assess the occurrence of muscular toxicity defined by an increase of CK up to 3-fold the upper superior limit without any evidence of member ischaemia.
• Vancomycin (VAN) treatment
Group VAN : Vancomycin intravenous treatment was initiated by a loading dose of 30 mg/kg in 1 hour and followed by a continuous maintenance infusion dosing between 15 and 30 mg/kg/d. The VAN dose was adapted to achieve a target serum vancomycin steady-state concentration of 20-30 mg/L assessed by a daily pharmacologic monitoring (therapeutic drug monitoring).

Locations

Country	Name	City	State
France	Uh Montpellier	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Acute Kidney Injury (AKI)	AKI stade 1, 2 or 3 according to KDIGO definition with baseline creatinine given by the last creatinine value before the start of treatment	7 days after the treatment initiation
Secondary	Incidence of Acute Kidney Injury (AKI)	AKI stade 1, 2 or 3 according to KDIGO definition with baseline creatinine given by the last creatinine value before the start of treatment	14 days after the treatment initiation
Secondary	Maximal decrease of glomerular filtration rate (GFR)	Decrease of GFR, estimated by CKD-EPI formula, from baseline as measured by all serum creatinine determinations during treatment	Through study treatment completion, an average of 2 weeks
Secondary	Incidence of severe renal failure	AKI stade 2 or 3 according to KDIGO definition or decrease of GFR more than 50% from baseline	Through study treatment completion, an average of 2 weeks
Secondary	Incidence of renal replacement therapy (RRT)	RRT initiated between the first and the last treatment administrations	Through study treatment completion, an average of 2 weeks
Secondary	Duration of RRT	Number of days between the first RRT initiation and the end of the last RRT during the ICU stay (excluding RRT performed in a dialysis center for chronic renal failure)	Through study completion limited to ICU stay, an average of 2 weeks
Secondary	Incidence of clinical treatment failure	defined by either persistent positive cultures, worsening of clinical status, death due to initial infection, or relapse after the end of treatment. It was assessed in case of documented GPC infection	15 days after the end of treatment
Secondary	Incidence of premature discontinuation of treatment	defined as a treatment stopped because of adverse event or clinical failure except death	Through study treatment completion, an average of 2 weeks
Secondary	Mortality	all cause mortality	28 days after treatment initiation
Secondary	Mortality	all cause mortality	6 months (180 days) after treatment initiation