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

NCT03961503 | Completed

• 1 other identifier: Q-2015-05-03
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

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

Keywords

Vancomycin; Daptomycin; Acute Kidney Injury; Nephrotoxicity; Infective Endocarditis; Foreign Body Associated Infection; Cardiovascular surgery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Incidence of Acute Kidney Injury (AKI)

  14 days after the treatment initiation

• Maximal decrease of glomerular filtration rate (GFR)

  Through study treatment completion, an average of 2 weeks

• Incidence of severe renal failure

  Through study treatment completion, an average of 2 weeks

• Incidence of renal replacement therapy (RRT)

  Through study treatment completion, an average of 2 weeks

• Duration of RRT

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

Study Arms (2)

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

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

Interventions

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.

Also known as: Group DAP

Daptomycin (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).

Also known as: Group VAN

Vancomycin (VAN)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Uh Montpellier

Montpellier, 34295, France

Location

Biospecimen

Retention: NONE RETAINED

Plasma: preoperative, ICU admission at POD0 and POD1 samples

MeSH Terms

Conditions

Endocarditis; Surgical Wound Infection; Mediastinitis; Acute Kidney Injury

Interventions

Daptomycin; Therapeutics; Vancomycin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Mediastinal Diseases; Thoracic Diseases; Respiratory Tract Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Glycopeptides; Glycoconjugates; Carbohydrates

Study Officials

• Philippe Gaudard, MD

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: May 23, 2019
• Study Start: January 1, 2016
• Primary Completion: January 30, 2016
• Study Completion: January 30, 2016
• Last Updated: May 23, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)