Severe InfectionNCT02846298
Evaluation of Pharmacokinetic / Pharmacodynamic Data and Interest Individualized Therapeutic Drug Monitoring Glycopeptides and β-lactam-aminoglycoside ICU
An observational study of Severe Infection, run by Fondation Hôpital Saint-Joseph at 1 site in France.
Trial summary
Since the discovery of streptomycin in 1944, aminoglycosides retain a remarkable bactericidal activity vis-à-vis including aerobic gram-negative bacilli. Thus, their synergistic effect with beta-lactams and their rapid bactericidal on many make unavoidable pathogens and make it a cornerstone of the treatment of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Infection
- What is being tested?
- Drug Monitoring
- How many people
- 172 participants
- Where
- 1 siteFrance
- Study dates
- 8 Nov 2015to 31 Dec 2023
- 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: All adult patients ≥ 18 years admitted to the intensive care unit of GH Paris Saint-Joseph and who will prescribe the entrance or during their stay an aminoglycoside treatment for severe infection
Who may be able to join
- Age w< 18 years old
- admitted in ICU unit for whom aminoglycoside treatment for severe infection was prescribed
Who cannot join
- Age less than 18 years
- Treatment with aminoglycoside off label
- Patient non hospitalized in intensive care
Trial locations and contacts
1 site in 1 country.
France1 site
Groupe Hospitalier Paris Saint Joseph
Paris, Île-de-France Region, 75014
About this study
Since the discovery of streptomycin in 1944, aminoglycosides retain a remarkable bactericidal activity vis-à-vis including aerobic gram-negative bacilli. Thus, their synergistic effect with beta-lactams and their rapid bactericidal on many make unavoidable pathogens and make it a cornerstone of the treatment of patients with severe sepsis or state of septic shock.
This is antibiotics exclusively parenteral administration. Their effectiveness is concentration-dependent and are administered by 30-minute infusion. Tolerance of venous is usually excellent. Their potential nephrotoxicity or cochleovestibular toxicity requires accurate monitoring of antibiotic residuals.
Read more
Moreover the fact that the effectiveness of the aminoglycosides is concentration dependent, the rate at the peak is decisive. A first sub-therapeutic dose leads to adaptively resistant bacteria compared to the aminoglycoside and therefore an increase of Minimal Inhibitory Concentrations (MIC). Many studies have been conducted in patients hospitalized in intensive care, highlighting underdoses in aminoglycosides when the prescribed dosages consistent with those used in non reanimated patients. Dr Moore showed in 89 ICU patients with bacteremia gram-negative bacilli, the relationship between the clinical course and obtaining whether therapeutic levels during the first administration of aminoglycosides. Thus, mortality in patients whose antibiotic concentrations to peak were subtherapeutic, amounted to 20.9% against 2.4% when concentrations were within the therapeutic range. In the context or an initial peak in the PK / PD ( Pharmacokinetic / Pharmacodynamic) objectives namely Cmax / MIC ≥ 8-10 desirable, individualized therapeutic drug monitoring and identification of factors that may cause a concentration of antibiotic at sub-therapeutic peak seems necessary , in patients for the majority an increased volume of distribution.
In addition to the β-lactams and glycopeptides, due to the increased volume of distribution in critically ill patients in sepsis, evaluation of serum 24 hours after starting treatment to check that the PK / PD goals for these molecules is achieved.
Read the detailed description
Primary / secondary objective
Investigators propose to conduct a study with the goal:
- Evaluate the rate of patients for whom efficacy endpoint PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses.
- Compare the 30-day mortality among patients with subclinical a first rate versus those who have reached the desired peak
- Evaluate the rate of patients for whom PK / PD efficiency target for related antibiotics is reached:
- Serum residual> 4X MIC for the β-lactam rate and continuous function of β-lactam and the germ.
- Serum between 25 and 35 mg / L vancomycin continuously.
- Assess the factors associated with obtaining a rate of aminoglycoside subtherapeutic peak in a population of critically ill patients.
- Assess the residual to 12h after injection to an anticipation of residual dosed at 24.
Methodology :
- Type Of study:
- Prospective, single-center type of professional practice evaluation
- Expected duration of the study six months
- Objective inclusion: 50 to 100 patients. Computing the number of patients to be included was done via the BioStaTGV software.
- Description Of the study (according to recommendations):
- Admission of patients in intensive care unit
- Levy peak aminoglycoside 30min after the end of the 30 minutes of infusion the first administration
- Collection of residual aminoglycoside to + 12h and between 23h-30 and 24 hours after injection.
- Extraction of the residual H + 24h, 30 min before injection to the β-lactam associated administered discontinuously or without time constraints if administration batchwise to the β-lactam and vancomycin.
- Routing unsettled and not frozen tubes in <2 hours of collection
- Reception and registration levy of the laboratory assay of anti-infective under his usual care as recommended service
- Determination of aminoglycoside and vancomycin immunoturbidimetric method (Indiko PLUS)
- Β-lactam assay by LC-MS
- Rendering the usual result (result server consultation for partial and report PDF available on the patient's medical record DXcare).
- Director-post of MIC of aminoglycoside and β-lactam vis-à-vis the offending germ for each bacterial strain isolated and documenting infection
- Destruction Levies: levies will not be retained after being used for the study. They will be destroyed in accordance with the rules of good practice research laboratories.
Data Monitoring and support:
Patient data will be collected on a computer CRF including clinical, biological and microbiological data of patients via the patient's medical record on DXcare: demographics, weight, height, BMI, hydration status, kidney function, liver function, shock, chronic heart failure, malnutrition, hypoalbuminemia burned, cirrhosis, chronic rheumatic disease, other antecedents, pregnancy, reason for hospitalization, etiology of sepsis motivating the introduction of aminoglycosides, β-lactam or glycopeptide and also other associated treatments. The data collected will help identify risk factors associated with a sub-therapeutic dosing aminoglycosides, β-lactam or glycopeptide.
- Conditions
- Severe Infection
- Being tested
- Drug Monitoring
- Keywords
- Drug Monitoring, ICU, Pharmacokinetic, Pharmacodynamic, antibiotic, Glycopeptides, β-lactam-aminoglycoside
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug MonitoringBiological
Evaluation of Pharmacokinetic / Pharmacodynamic Data and Interest Individualized Therapeutic Drug Monitoring Glycopeptides and β-lactam-aminoglycoside ICU
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Pharmacokinetic Glycopeptides Cmax
Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses
Measured: 30 minutes after first injection
Assessment of Pharmacodynamic Glycopeptides Cmax
Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses
Measured: 30 minutes after first injection
Assessment of Pharmacokinetic β-lactam-aminoglycoside Cmax
Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses
Measured: 30 minutes after first injection
Assessment of Pharmacodynamic β-lactam-aminoglycoside Cmax
Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses
Measured: 30 minutes after first injection
Secondary outcomes (3)
Mortality rate
Compare the 30-day mortality among patients with subclinical a first rate versus those who have reached the desired peak
Measured: Day 30
Assess the residual of Glycopeptides
Assess the residual to 12h after injection to an anticipation of residual dosed at 24.
Measured: Hour 12 and Hour 24 after injection
Assess the residual of β-lactam-aminoglycoside
Assess the residual to 12h after injection to an anticipation of residual dosed at 24.
Measured: Hour 12 and Hour 24 after injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2016 (estimated)
- Study start8 Nov 2015
- Primary completion22 Oct 2018
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe InfectionStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondation Hôpital Saint-Joseph
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippart Francois, MD, Principal investigator, Fondation Hôpital Saint-Joseph
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02846298
- Sponsor's protocol ID
- PKPD AG-BL
- Status last verified
- Apr 2023
- First submitted
- 20 Jul 2016
- Last updated
- 27 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Pharmacokinetic / Pharmacodynamic Data and Interest Individualized Therapeutic Drug Monitoring Glycopeptides and β-lactam-aminoglycoside ICU
- ClinicalTrials.gov ID
- NCT02846298
- Acronym / sponsor ID
- PKPD AG-BL
- Conditions
- Severe Infection
- Keywords
- Drug Monitoring, ICU, Pharmacokinetic, Pharmacodynamic, antibiotic, Glycopeptides, β-lactam-aminoglycoside
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 172 participants (actual)
- Lead sponsor
- Fondation Hôpital Saint-JosephUniversity, hospital or other
- Study start
- 8 Nov 2015 (actual)
- Primary completion
- 22 Oct 2018 (actual)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 27 Jul 2016 (estimated)
- 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.
Since the discovery of streptomycin in 1944, aminoglycosides retain a remarkable bactericidal activity vis-à-vis including aerobic gram-negative bacilli. Thus, their synergistic effect with beta-lactams and their rapid bactericidal on many make unavoidable pathogens and make it a cornerstone of the treatment of patients with severe sepsis or state of septic shock.
This is antibiotics exclusively parenteral administration. Their effectiveness is concentration-dependent and are administered by 30-minute infusion. Tolerance of venous is usually excellent. Their potential nephrotoxicity or cochleovestibular toxicity requires accurate monitoring of antibiotic residuals.
Moreover the fact that the effectiveness of the aminoglycosides is concentration dependent, the rate at the peak is decisive. A first sub-therapeutic dose leads to adaptively resistant bacteria compared to the aminoglycoside and therefore an increase of Minimal Inhibitory Concentrations (MIC). Many studies have been conducted in patients hospitalized in intensive care, highlighting underdoses in aminoglycosides when the prescribed dosages consistent with those used in non reanimated patients. Dr Moore showed in 89 ICU patients with bacteremia gram-negative bacilli, the relationship between the clinical course and obtaining whether therapeutic levels during the first administration of aminoglycosides. Thus, mortality in patients whose antibiotic concentrations to peak were subtherapeutic, amounted to 20.9% against 2.4% when concentrations were within the therapeutic range. In the context or an initial peak in the PK / PD ( Pharmacokinetic / Pharmacodynamic) objectives namely Cmax / MIC ≥ 8-10 desirable, individualized therapeutic drug monitoring and identification of factors that may cause a concentration of antibiotic at sub-therapeutic peak seems necessary , in patients for the majority an increased volume of distribution.
In addition to the β-lactams and glycopeptides, due to the increased volume of distribution in critically ill patients in sepsis, evaluation of serum 24 hours after starting treatment to check that the PK / PD goals for these molecules is achieved.
Detailed description
Primary / secondary objective
Investigators propose to conduct a study with the goal:
- Evaluate the rate of patients for whom efficacy endpoint PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses.
- Compare the 30-day mortality among patients with subclinical a first rate versus those who have reached the desired peak
- Evaluate the rate of patients for whom PK / PD efficiency target for related antibiotics is reached:
- Serum residual> 4X MIC for the β-lactam rate and continuous function of β-lactam and the germ.
- Serum between 25 and 35 mg / L vancomycin continuously.
- Assess the factors associated with obtaining a rate of aminoglycoside subtherapeutic peak in a population of critically ill patients.
- Assess the residual to 12h after injection to an anticipation of residual dosed at 24.
Methodology :
- Type Of study:
- Prospective, single-center type of professional practice evaluation
- Expected duration of the study six months
- Objective inclusion: 50 to 100 patients. Computing the number of patients to be included was done via the BioStaTGV software.
- Description Of the study (according to recommendations):
- Admission of patients in intensive care unit
- Levy peak aminoglycoside 30min after the end of the 30 minutes of infusion the first administration
- Collection of residual aminoglycoside to + 12h and between 23h-30 and 24 hours after injection.
- Extraction of the residual H + 24h, 30 min before injection to the β-lactam associated administered discontinuously or without time constraints if administration batchwise to the β-lactam and vancomycin.
- Routing unsettled and not frozen tubes in <2 hours of collection
- Reception and registration levy of the laboratory assay of anti-infective under his usual care as recommended service
- Determination of aminoglycoside and vancomycin immunoturbidimetric method (Indiko PLUS)
- Β-lactam assay by LC-MS
- Rendering the usual result (result server consultation for partial and report PDF available on the patient's medical record DXcare).
- Director-post of MIC of aminoglycoside and β-lactam vis-à-vis the offending germ for each bacterial strain isolated and documenting infection
- Destruction Levies: levies will not be retained after being used for the study. They will be destroyed in accordance with the rules of good practice research laboratories.
Data Monitoring and support:
Patient data will be collected on a computer CRF including clinical, biological and microbiological data of patients via the patient's medical record on DXcare: demographics, weight, height, BMI, hydration status, kidney function, liver function, shock, chronic heart failure, malnutrition, hypoalbuminemia burned, cirrhosis, chronic rheumatic disease, other antecedents, pregnancy, reason for hospitalization, etiology of sepsis motivating the introduction of aminoglycosides, β-lactam or glycopeptide and also other associated treatments. The data collected will help identify risk factors associated with a sub-therapeutic dosing aminoglycosides, β-lactam or glycopeptide.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All adult patients ≥ 18 years admitted to the intensive care unit of GH Paris Saint-Joseph and who will prescribe the entrance or during their stay an aminoglycoside treatment for severe infection
Key inclusion criteria (2 listed)
- Age w< 18 years old
- admitted in ICU unit for whom aminoglycoside treatment for severe infection was prescribed
Key exclusion criteria (3 listed)
- Age less than 18 years
- Treatment with aminoglycoside off label
- Patient non hospitalized in intensive care
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 |
|---|---|---|
| Drug MonitoringEvaluation of Pharmacokinetic / Pharmacodynamic Data and Interest Individualized Therapeutic Drug Monitoring Glycopeptides and β-lactam-aminoglycoside ICU | Biological | – |
Primary outcome
Assessment of Pharmacokinetic Glycopeptides Cmax
Time frame: 30 minutes after first injection
Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses
Assessment of Pharmacodynamic Glycopeptides Cmax
Time frame: 30 minutes after first injection
Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses
Assessment of Pharmacokinetic β-lactam-aminoglycoside Cmax
Time frame: 30 minutes after first injection
Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses
Assessment of Pharmacodynamic β-lactam-aminoglycoside Cmax
Time frame: 30 minutes after first injection
Evaluate the rate of patients for whom the objective of efficiency PK / PD Cmax / MIC ≥ 8-10 is reached at the first dose of the usual doses
3 secondary outcomes
Mortality rate
Time frame: Day 30
Assess the residual of Glycopeptides
Time frame: Hour 12 and Hour 24 after injection
Assess the residual of β-lactam-aminoglycoside
Time frame: Hour 12 and Hour 24 after injection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2023.
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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.
Philippart Francois, MD principal investigator
Fondation Hôpital Saint-Joseph
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 Severe Infection, run by Fondation Hôpital Saint-Joseph 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 2 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 27 Apr 2023. 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?
Results are not available in the source record.
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?
Assessment of Pharmacokinetic Glycopeptides Cmax (time frame: 30 minutes after first injection). The study lists 4 primary outcomes in all. 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 27 Apr 2023.