Renal Failure Chronic Requiring HemodialysisPhase 4DIAMSNCT01982864
Pharmacokinetics of an Aminoglycoside in Hemodialysis Patients.
A Phase 4 study testing Gentamicin in people with Renal Failure Chronic Requiring Hemodialysis, run by University Hospital, Limoges at 2 sites in France.
Trial summary
Aminoglycosides are widely used for the treatment of Gram-negative bacilli and Staphylococcus aureus infections because of their effectiveness and low cost. Nevertheless, many aspects of their optimal use in hemodialysis patients remain unsolved and little is known about their pharmacokinetics in this context. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Failure Chronic Requiring Hemodialysis
- What is being tested?
- Gentamicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesFrance
- Study dates
- Oct 2013to Jan 2016
- Phase
- Phase 4
- 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
Who may be able to join
- age upper to 18 years
- Patients hospitalized in the "Service de Néphrologie - Hémodialyse, Transplantations, CHU de Limoges"
- Patients requiring chronic hemodialysis
- Patients requiring a treatment by aminoglycosides
- Patients willing to give their written informed consent for their participation to the study
- Patients affiliated to the French social security system or equivalent
Who cannot join
- Patients under legal protection
- Patients unable or unwilling to provide informed consent and not under legal protection
- Patients deprived of liberty
- Contraindications to gentamicin
- Pregnant or breast-feeding women or women of childbearing potential without efficient contraception (based on declaration)
- Patients with any altered mental status or any psychiatric condition that would interfere with the understanding of the study
- Patients enrolled in another clinical trial testing drugs or therapeutic strategies
Trial locations and contacts
2 sites in 1 country.
France2 sites
CHU LIMOGES - Laboratoire de Pharmacologie
Limoges, 87042
CHU LIMOGES - Service Néphrologie
Limoges, 87042
About this study
Aminoglycosides are widely used for the treatment of Gram-negative bacilli and Staphylococcus aureus infections because of their effectiveness and low cost. Nevertheless, many aspects of their optimal use in hemodialysis patients remain unsolved and little is known about their pharmacokinetics in this context. The current practice for prescribing aminoglycosides to these particular patients consists in giving after each hemodialysis session about half the dose usually given to patients with normal renal function.
However, theoretical considerations and emerging clinical data suggest that this may not be the most beneficial dosing regimen as efficient peak concentrations are often not attained and the occurrence of ototoxicity and nephrotoxicity is still frequent.
Read the detailed description
Recent evidence about the pharmacokinetics and pharmacodynamics of aminoglycosides strongly supports administration of aminoglycosides before, rather than after, hemodialysis. Therapeutic drug monitoring using pharmacokinetic modeling is currently used in non-hemodialysis patients. However, the PK tools employed are not suitable to dialysis patients.
For aminoglycosides, the ratio of peak to Minimal Inhibitory Concentration (MIC) has been shown to be the parameter that best correlates with clinical efficacy, whilst prolonged exposure to high concentrations have been related to either nephrotoxicity or ototoxicity. Additionally, aminoglycosides are mostly excreted as unchanged drugs in urine and their clearance is directly proportional to the glomerular filtration rate. The elimination half-life of aminoglycosides is approximately 1.5-3 hours in adults with normal renal function, but is greatly prolonged up to 36-70 hours in patients with end-stage renal failure. In a standard patient, aminoglycosides are administered as a single dose, over a short time interval, to obtain an elevated blood peak concentration (the effective level). The next injection is not administered before 24 hours, to allow the patient to wash out the aminoside and to minimize the residual blood concentration (the toxic level). The aim here is to maximize the peak concentration during a fair amount of time (by repeating the peaks) and to minimize the overall drug exposure, responsible for the toxicity.
For the renal impaired patient, our hypothesis is that the hemodialyzer can be regarded as a kidney. Thus, the administration of the aminoside at the beginning of the hemodialysis could lead to profiles of elimination comparable to those observed in normorenal patients.
The research aims at performing a population pharmacokinetic (POPPK) study of gentamicin when given to hemodialysis patients.
- Being tested
- Gentamicin
- Keywords
- Aminoglycosides, hemodialysis, clinical pharmacokinetics, pharmacokinetic modelling, Bayesian estimation, Necessity, of the treatment, gentamicin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GentamicinDrug
The decision to introduce the antibiotic is made during a session or between two sessions according to both the clinicians usual procedure.
Depending on the number of injections, 8 to 10 blood samples will be drawn per patient. Clinical and biological data will be concomitantly collected (e.g., hemodialysis session duration, creatinine clearance…).
The number of blood sampling and the time schedule will be adapted to the prescription and the possible follow-up of the treatment after the first injection. Whatever the time is between the first injection and the following dialysis session, a sampling will be performed 30 minutes after the end of the injection (T1), 8h after the end of the injection (T2), juste before (TAD), in the middle (TMD) and at the end of the dialysis (TFD).
| Study group | Role | What they receive |
|---|---|---|
| hemodialysis patients | Experimental | The administration of gentamicin at the beginning of the hemodialysis. Receives: Drug: Gentamicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration curves of gentamicin
The research aims at performing a population pharmacokinetic (POPPK) study of gentamicin when given to hemodialysis patients.
The ability to describe the concentration curves versus time (Biais (%) between the observed concentrations and the concentrations predicted by the model).
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2013 (estimated)
- Study startOct 2013
- Primary completionJan 2016
- Study completionJan 2016
Why it stopped: Not enough patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal Failure Chronic Requiring HemodialysisStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre MARQUET, MD, Principal investigator, CHU LIMOGES
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01982864
- Sponsor's protocol ID
- I12008 DIAMS
- Acronym
- DIAMS
- Status last verified
- Jul 2020
- First submitted
- 31 Oct 2013
- Last updated
- 17 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Franck B, Monchaud C, Saint-Marcoux F, Rerolle JP, Allard J, Allot V, Marquet P, Essig M, Woillard JB. Population pharmacokinetics of gentamicin in haemodialysis patients: modelling, simulations and recommendations. Eur J Clin Pharmacol. 2020 Jul;76(7):947-955. doi: 10.1007/s00228-020-02867-3. Epub 2020 May 1.
PubMed 32358683
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of an Aminoglycoside in Hemodialysis Patients.
- ClinicalTrials.gov ID
- NCT01982864
- Acronym / sponsor ID
- DIAMS / I12008 DIAMS
- Keywords
- Aminoglycosides, hemodialysis, clinical pharmacokinetics, pharmacokinetic modelling, Bayesian estimation, Necessity, of the treatment, gentamicin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not enough patients
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 13 Nov 2013 (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.
Aminoglycosides are widely used for the treatment of Gram-negative bacilli and Staphylococcus aureus infections because of their effectiveness and low cost. Nevertheless, many aspects of their optimal use in hemodialysis patients remain unsolved and little is known about their pharmacokinetics in this context. The current practice for prescribing aminoglycosides to these particular patients consists in giving after each hemodialysis session about half the dose usually given to patients with normal renal function.
However, theoretical considerations and emerging clinical data suggest that this may not be the most beneficial dosing regimen as efficient peak concentrations are often not attained and the occurrence of ototoxicity and nephrotoxicity is still frequent.
Detailed description
Recent evidence about the pharmacokinetics and pharmacodynamics of aminoglycosides strongly supports administration of aminoglycosides before, rather than after, hemodialysis. Therapeutic drug monitoring using pharmacokinetic modeling is currently used in non-hemodialysis patients. However, the PK tools employed are not suitable to dialysis patients.
For aminoglycosides, the ratio of peak to Minimal Inhibitory Concentration (MIC) has been shown to be the parameter that best correlates with clinical efficacy, whilst prolonged exposure to high concentrations have been related to either nephrotoxicity or ototoxicity. Additionally, aminoglycosides are mostly excreted as unchanged drugs in urine and their clearance is directly proportional to the glomerular filtration rate. The elimination half-life of aminoglycosides is approximately 1.5-3 hours in adults with normal renal function, but is greatly prolonged up to 36-70 hours in patients with end-stage renal failure. In a standard patient, aminoglycosides are administered as a single dose, over a short time interval, to obtain an elevated blood peak concentration (the effective level). The next injection is not administered before 24 hours, to allow the patient to wash out the aminoside and to minimize the residual blood concentration (the toxic level). The aim here is to maximize the peak concentration during a fair amount of time (by repeating the peaks) and to minimize the overall drug exposure, responsible for the toxicity.
For the renal impaired patient, our hypothesis is that the hemodialyzer can be regarded as a kidney. Thus, the administration of the aminoside at the beginning of the hemodialysis could lead to profiles of elimination comparable to those observed in normorenal patients.
The research aims at performing a population pharmacokinetic (POPPK) study of gentamicin when given to hemodialysis patients.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| hemodialysis patients | Experimental | Drug: GentamicinThe administration of gentamicin at the beginning of the hemodialysis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- age upper to 18 years
- Patients hospitalized in the "Service de Néphrologie - Hémodialyse, Transplantations, CHU de Limoges"
- Patients requiring chronic hemodialysis
- Patients requiring a treatment by aminoglycosides
- Patients willing to give their written informed consent for their participation to the study
Key exclusion criteria (7 listed)
- Patients under legal protection
- Patients unable or unwilling to provide informed consent and not under legal protection
- Patients deprived of liberty
- Contraindications to gentamicin
- Pregnant or breast-feeding women or women of childbearing potential without efficient contraception (based on declaration)
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 |
|---|---|---|
| GentamicinThe decision to introduce the antibiotic is made during a session or between two sessions according to both the clinicians usual procedure. Depending on the number of injections, 8 to 10 blood samples will be drawn per patient. Clinical and biological data will be concomitantly collected (e.g., hemodialysis session duration, creatinine clearance…). The number of blood sampling and the time schedule will be adapted to the prescription and the possible follow-up of the treatment after the first injection. Whatever the time is between the first injection and the following dialysis session, a sampling will be performed 30 minutes after the end of the injection (T1), 8h after the end of the injection (T2), juste before (TAD), in the middle (TMD) and at the end of the dialysis (TFD). | Drug | hemodialysis patients |
Primary outcome
Concentration curves of gentamicin
Time frame: 1 week
The research aims at performing a population pharmacokinetic (POPPK) study of gentamicin when given to hemodialysis patients. The ability to describe the concentration curves versus time (Biais (%) between the observed concentrations and the concentrations predicted by the model).
Results and safety
The study was stopped early (reason given: Not enough patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2020.
- Results publication: PubMed 32358683Franck B, Monchaud C, Saint-Marcoux F, Rerolle JP, Allard J, Allot V, Marquet P, Essig M, Woillard JB. Population pharmacokinetics of gentamicin in haemodialysis patients: modelling, simulations and recommendations. Eur J Clin Pharmacol. 2020 Jul;76(7):947-955. doi: 10.1007/s00228-020-02867-3. Epub 2020 May 1.
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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.
Pierre MARQUET, MD principal investigator
CHU LIMOGES
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Gentamicin in people with Renal Failure Chronic Requiring Hemodialysis, run by University Hospital, Limoges at 2 sites 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 6 inclusion and 7 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: stopped early, as of the sponsor's last update on 17 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Not enough patients). 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?
Concentration curves of gentamicin (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01982864, which also lists 1 linked publication.
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 17 Jul 2020.