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

NCT ID: NCT03961503

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 72 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-01-01
• Study Completion Date: 2016-01-30

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.

Conditions

Infective Endocarditis; Infection Related to Ventricular Assist Device; Infection Related to Vascular Prothesis; Surgical Site Infection; Mediastinitis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Daptomycin (DAP)

DAP : Cohort of patients who received daptomycin as the first line treatment for at least 48 hours for the defined indication

Daptomycin (DAP) treatment

Intervention Type: DRUG

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)

VAN : Cohort of patients who received vancomycin as the first line treatment for at least 48 hours for the defined indication

Vancomycin (VAN) treatment

Intervention Type: DRUG

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).

Interventions

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.

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Group DAP; Group VAN

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Gaudard, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Locations

Uh Montpellier

Montpellier, , France

Countries

France

Other Identifiers

Q-2015-05-03

Identifier Type: -

Identifier Source: org_study_id