Infective EndocarditisDVNNCT03961503
Retrospective Analysis of Nephrotoxicity During Daptomycin Versus Vancomycin Treatments in High Risk Patients
An observational study of Infective Endocarditis and Infection Related to Ventricular Assist Device, run by University Hospital, Montpellier at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infective Endocarditis, Infection Related to Ventricular Assist Device, Infection Related to Vascular Prothesis
- What is being tested?
- Daptomycin (DAP) treatment and Vancomycin (VAN) treatment
- Type of treatment
- Injection or infusion
- How many people
- 72 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2016to 30 Jan 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patient admitted in Intensive Care Unit before and/or after cardiovascular surgery with at least one organ failure
Who may be able to join
- 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)
Who cannot join
- Prophylaxis indication of antibiotics
- Kidney disease on chronic dialysis
- Acute onset of RRT before initiation of DAP or VAN treatment
- Staphylococcus pneumonia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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
- Being tested
- Daptomycin (DAP) treatment, Vancomycin (VAN) treatment
- Keywords
- Vancomycin, Daptomycin, Acute Kidney Injury, Nephrotoxicity, Infective Endocarditis, Foreign Body Associated Infection, Cardiovascular surgery
- Medical subject headings
- Endocarditis, Surgical Wound Infection, Mediastinitis, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daptomycin (DAP) treatmentDrug
Also called Group DAP
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) treatmentDrug
Also called Group VAN
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).
| Study group | Role | What they receive |
|---|---|---|
| Daptomycin (DAP) | DAP : Cohort of patients who received daptomycin as the first line treatment for at least 48 hours for the defined indication Receives: 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 Receives: Drug: Vancomycin (VAN) treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 7 days after the treatment initiation
Secondary outcomes (9)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: Through study treatment completion, an average of 2 weeks
Mortality
all cause mortality
Measured: 28 days after treatment initiation
Mortality
all cause mortality
Measured: 6 months (180 days) after treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2019
- Study start1 Jan 2016
- Primary completion30 Jan 2016
- Study completion30 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infective EndocarditisStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippe Gaudard, MD, Principal investigator, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03961503
- Sponsor's protocol ID
- Q-2015-05-03
- Acronym
- DVN
- Status last verified
- May 2019
- First submitted
- 16 May 2019
- Last updated
- 23 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Kidney Injury During Daptomycin Versus Vancomycin Treatment in Cardiovascular Critically Ill Patients: a Propensity Score Matched Analysis
- ClinicalTrials.gov ID
- NCT03961503
- Acronym / sponsor ID
- DVN / Q-2015-05-03
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 1 Jan 2016 (actual)
- Primary completion
- 30 Jan 2016 (actual)
- Study completion
- 30 Jan 2016 (actual)
- First posted
- 23 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daptomycin (DAP) | – | Drug: Daptomycin (DAP) treatmentDAP : Cohort of patients who received daptomycin as the first line treatment for at least 48 hours for the defined indication |
| Vancomycin (VAN) | – | Drug: Vancomycin (VAN) treatmentVAN : Cohort of patients who received vancomycin as the first line treatment for at least 48 hours for the defined indication |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient admitted in Intensive Care Unit before and/or after cardiovascular surgery with at least one organ failure
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (4 listed)
- Prophylaxis indication of antibiotics
- Kidney disease on chronic dialysis
- Acute onset of RRT before initiation of DAP or VAN treatment
- Staphylococcus pneumonia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daptomycin (DAP) treatmentAlso: Group DAPGroup 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. | Drug | Daptomycin (DAP) |
| Vancomycin (VAN) treatmentAlso: Group VANGroup 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). | Drug | Vancomycin (VAN) |
Primary outcome
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
9 secondary outcomes
Incidence of Acute Kidney Injury (AKI)
Time frame: 14 days after the treatment initiation
Maximal decrease of glomerular filtration rate (GFR)
Time frame: Through study treatment completion, an average of 2 weeks
Incidence of severe renal failure
Time frame: Through study treatment completion, an average of 2 weeks
Incidence of renal replacement therapy (RRT)
Time frame: Through study treatment completion, an average of 2 weeks
Duration of RRT
Time frame: Through study completion limited to ICU stay, an average of 2 weeks
Incidence of clinical treatment failure
Time frame: 15 days after the end of treatment
Incidence of premature discontinuation of treatment
Time frame: Through study treatment completion, an average of 2 weeks
Mortality
Time frame: 28 days after treatment initiation
Mortality
Time frame: 6 months (180 days) after treatment initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe Gaudard, MD principal investigator
University Hospital, Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infective Endocarditis and Infection Related to Ventricular Assist Device, run by University Hospital, Montpellier at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Acute Kidney Injury (AKI) (time frame: 7 days after the treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2019.