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

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

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.

Study Overview

• Status: Completed
• Conditions: Surgical Site Infection; Infective Endocarditis; Mediastinitis; Infection Related to Ventricular Assist Device; Infection Related to Vascular Prothesis
• Intervention / Treatment: Drug: Daptomycin (DAP) treatment; Drug: Vancomycin (VAN) treatment

• Study Type: Observational
• Enrollment (Actual): 72

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • UH Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Daptomycin (DAP); DAP : Cohort of patients who received daptomycin as the first line treatment for at least 48 hours for the defined indication	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.; Other Names: Group DAP
Vancomycin (VAN); VAN : Cohort of patients who received vancomycin as the first line treatment for at least 48 hours for the defined indication	Drug: 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).; Other Names: Group VAN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
Mortality	all cause mortality	28 days after treatment initiation
Mortality	all cause mortality	6 months (180 days) after treatment initiation

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Philippe Gaudard, MD, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): January 30, 2016
• Study Completion (Actual): January 30, 2016

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 22, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Actual): May 23, 2019
• Last Update Submitted That Met QC Criteria: May 22, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Vancomycin; Acute Kidney Injury; Nephrotoxicity; Daptomycin; Cardiovascular surgery; Infective Endocarditis; Foreign Body Associated Infection
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Postoperative Complications; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Wound Infection; Cardiovascular Infections; Mediastinal Diseases; Thoracic Diseases; Infections; Communicable Diseases; Surgical Wound Infection; Endocarditis, Bacterial; Endocarditis; Mediastinitis; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Daptomycin
• Other Study ID Numbers: Q-2015-05-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No