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NCT Number: NCT03961503

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

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.

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Key information

Conditions

Infective Endocarditis Acute Kidney Injury Cardiovascular Diseases Endocarditis Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Heart Diseases Infection Related to Vascular Prothesis Infection Related to Ventricular Assist Device Infections Kidney Diseases Male Urogenital Diseases Mediastinal Diseases Mediastinitis Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Renal Insufficiency Respiratory Tract Diseases Surgical Site Infection Surgical Wound Infection Thoracic Diseases Urogenital Diseases Urologic Diseases Wound Infection

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Uh Montpellier

Montpellier, 34295, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Daptomycin (DAP) treatment

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.

Other names: Group DAP

Vancomycin (VAN) treatment

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).

Other names: Group VAN

Primary outcomes

  1. Incidence of Acute Kidney Injury (AKI)

    Time frame: 7 days after the treatment initiation

    AKI stade 1, 2 or 3 according to KDIGO definition with baseline creatinine given by the last creatinine value before the start of treatment

Secondary outcomes

  1. Incidence of Acute Kidney Injury (AKI)

    Time frame: 14 days after the treatment initiation

    AKI stade 1, 2 or 3 according to KDIGO definition with baseline creatinine given by the last creatinine value before the start of treatment

  2. Maximal decrease of glomerular filtration rate (GFR)

    Time frame: Through study treatment completion, an average of 2 weeks

    Decrease of GFR, estimated by CKD-EPI formula, from baseline as measured by all serum creatinine determinations during treatment

  3. Incidence of severe renal failure

    Time frame: Through study treatment completion, an average of 2 weeks

    AKI stade 2 or 3 according to KDIGO definition or decrease of GFR more than 50% from baseline

  4. Incidence of renal replacement therapy (RRT)

    Time frame: Through study treatment completion, an average of 2 weeks

    RRT initiated between the first and the last treatment administrations

  5. Duration of RRT

    Time frame: Through study completion limited to ICU stay, an average of 2 weeks

    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)

  6. Incidence of clinical treatment failure

    Time frame: 15 days after the end of treatment

    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

  7. Incidence of premature discontinuation of treatment

    Time frame: Through study treatment completion, an average of 2 weeks

    defined as a treatment stopped because of adverse event or clinical failure except death

  8. Mortality

    Time frame: 28 days after treatment initiation

    all cause mortality

  9. Mortality

    Time frame: 6 months (180 days) after treatment initiation

    all cause mortality

Sponsors and collaborators

Lead sponsor

University Hospital, Montpellier

Other

Registry information

Official study title

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

Acronym: DVN

Important dates

Study start
2016
Primary completion
2016
Study completion
2016
First posted
May 23, 2019
Registry last updated
May 23, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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