Gram-Negative Bacterial InfectionsPhase 4NCT02285075
Temocillin Pharmacokinetic in Hemodialysis
A Phase 4 study testing temocillin PK/PD in haemodialysis in people with Gram-Negative Bacterial Infections and Renal Failure Chronic Requiring Hemodialysis, run by AZ Sint-Jan AV at 2 sites in Belgium.
Trial summary
The current study aimed to explore the pharmacokinetics of temocillin in patients treated with haemodialysis and to demonstrated whether or not the pharmacodynamics target of a time above a MIC of 16 mg/L of more than 40 and 60 % of the dosing interval could be obtained with a dosing schedule of 1 gram/24 hours, 2… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gram-Negative Bacterial Infections, Renal Failure Chronic Requiring Hemodialysis
- What is being tested?
- temocillin PK/PD in haemodialysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesBelgium
- Study dates
- Jun 2011to Dec 2014
- 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
- all patients under treatment with haemodialysis for ESRD for whom a treatment with temocillin was indicated according to the attending physician were eligible for the study.
Who cannot join
- an age of less than 18 years
- an estimated life-expectance of < 24 hours due to major co-morbid conditions
- pregnancy
- an IgE-mediated allergy to penicillins
- patients not giving informed consent.
Trial locations and contacts
2 sites in 1 country.
Belgium2 sites
AZ Sint-Jan Brugge Oostende AV
Bruges, 8000
Louvain Drug Research Institute (LDRI)
Brussels, 1020
About this study
Official title: A Clinical Pharmacokinetic Study: Is Three Times Weekly Temocillin Appropriate for the Treatment of Severe Gram-negative Infections in Patients With ESRD Treated With Intermittent Hemodialysis?
The current study aimed to explore the pharmacokinetics of temocillin in patients treated with haemodialysis and to demonstrated whether or not the pharmacodynamics target of a time above a MIC of 16 mg/L of more than 40 and 60 % of the dosing interval could be obtained with a dosing schedule of 1 gram/24 hours, 2 gram/48 hours and 3 gram/72 hours, all of these doses given after haemodialysis sessions only.
Read the detailed description
Background: Temocillin is a renally cleared penicillin with long serum half-live and potent activity against most gram-negative bacteria, making it an ideal candidate for treatment given on dialysis days only of severe gram-negative infections in patients with ESRD treated with haemodialysis.
Endpoints:
Primary: The current study aimed to demonstrated by measurement of AUC whether or not the pharmacodynamics target of a time above a MIC of 8 and 16 mg/L of more than 40 and 60 % of the dosing interval could be obtained with a dosing schedule of 1 gram/24 hours, 2 gram/48 hours and 3 gram/72 hours, all of these doses given after haemodialysis sessions only.
Secondary: Key pharmacokinetic and dialytic parameters were determined as previously described16. The following parameters were recorded: the volume of distribution Vd (determined as Vd = dose / (Tempeak - Temtrough) in liter); the Vd/Wt (in liter/kg body weight); the non-dialysis clearance of temocillin (Ke(non-dialysis) = [ln(Tempeak) - ln(Tempre)] / time between peak level and start of next dialysis); the non-dialysis half-life (T1/2(non-dialysis) = 0.693 / Ke(non-dialysis) in hours); the dialysis clearance of temocillin (Ke(dialysis) = [ln(Tempre) - ln(Tempost)] / dialysis duration); the dialysis half-life (T1/2(dialysis) = 0.693 / Ke(dialysis) in hours); the Urea Reduction Ratio (URR = (BUNpre - BUNpost) / BUNpre); the Temocillin Reduction Ratio TRR = (Tempre - Tempost) / Tempre); the Temocillin Removal Ratio (the total amount of temocillin recovered in the dialysate, based on the area under the curve of the temocillin removal rate and the treatment time); and the AUC of temocillin. For all PK/PD analysis, the non-compartmental method using RStudio 0.98.501 with R 3.0.2 software was used.
Methods: Pharmacokinetic study measuring total and free temocillin concentrations in patients treated with intermittent haemodialysis and temocillin. Blood samples were drawn just before, and at 0.5, 3, 6, 12, 20 (before dialysis) and 24 (at the end of dialysis) hours after start of the infusion when patients were dialysed with a 1-day interval; just before and at 0.5, 3, 6, 12, 24, 36, 44 (before dialysis) and 48 (at the end of dialysis) hours after start of the infusion when patients were dialysed with a 2-day interval, and just before and at 0.5, 3, 6, 12, 24, 36, 48, 68 (before dialysis) and 72 (at the end of dialysis) hours after start of the infusion if patients were dialysed with a 3-day interval. Patients were followed for 1 to 6 subsequent AUC. Dialysate samples were taken 1, 2, 3 and 4 h after the start of dialysis. All samples were taken from an arterial or venous catheter, after thorough rinsing. Serum (obtained by centrifugation after blood clotting) and dialysate was frozen (-80 C) immediately after sampling until analysis.
Temocillin total and free concentrations were determined with high performance liquid chromotography(HPLC) with a LiChrospher 100 RP-18 5 μm column (Merck AG), using an elution buffer 100 mM Na acetate buffer pH 7/acetonitrile (95:5, v/v), a flow rate 1 mL/min and a Waters 2690 Alliance System (Waters Corp., Milford, MA, USA), with quantification at 235 nm as previously described.
- Being tested
- temocillin PK/PD in haemodialysis
- Keywords
- temocillin, PD/PD, T>MIC
- Medical subject headings
- Gram-Negative Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
temocillin PK/PD in haemodialysisDrug
Pharmacokinetic study measuring total and free temocillin concentrations just before, and at 0.5, 3, 6, 12, 20 (before dialysis) and 24 (at the end of dialysis) hours after start of the infusion when patients were dialysed with a 1-day interval; just before and at 0.5, 3, 6, 12, 24, 36, 44 (before dialysis) and 48 (at the end of dialysis) hours after start of the infusion when patients were dialysed with a 2-day interval, and just before and at 0.5, 3, 6, 12, 24, 36, 48, 68 (before dialysis) and 72 (at the end of dialysis) hours after start of the infusion if patients were dialysed with a 3-day interval in order to determine basic PK and PD parameters in patients treated with intermittent haemodialysis and temocillin (Vd, T1/2, protein binding, clearance, reduction rate and T > MIC of 8 and 16 mg/L).
| Study group | Role | What they receive |
|---|---|---|
| temocillin PK/PD in haemodialysis | Other | Pharmacokinetic study measuring total and free temocillin concentrations in patients treated with haemodialysis receiving 1 gram temocillin for a 1 day interval, 2 gram temocillin for a two day interval and 3 gram temocillin for a 3 day interval to the next dialysis session Receives: Drug: temocillin PK/PD in haemodialysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
% of the dosing interval time above an MIC of 8 and 16 mg/L (% T>MIC 8 or 16 mg/L)
Is T > MIC 8 and 16 mg/ML > 40 or 60 %
Measured: two to ten days
Secondary outcomes (6)
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Vd (volume of distribution)
Measured: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
T1/2 (serum half life, on and of dialysis)
Measured: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Temocillin clearance (renal and non-renal)
Measured: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Temocillin reduction rate
Measured: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
temocillin removal rate
Measured: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
temocillin protein binding
Measured: two to ten days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2014 (estimated)
- Study startJun 2011
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gram-Negative Bacterial InfectionsStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- AZ Sint-Jan AV
- Sponsor type
- University, hospital or other
- Collaborators
- Paul Tulkens, Louvain drug research institute, belgium, Francoise Van Bambeke, Louvain drug research institute, belgium, Ana Miranda Bastos, Louvain drug research institute, belgium
- Responsible party
- Principal investigator, Vandecasteele Stefaan Johan, AZ Sint-Jan AV
- Investigators
- Stefaan J Vandecasteele, MD, PhD, Principal investigator, AZ Sint-Jan AV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02285075
- Sponsor's protocol ID
- SVDC Temocillin 1
- Status last verified
- Jan 2016
- First submitted
- 2 Nov 2014
- Last updated
- 5 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Miranda Bastos AC, Vandecasteele SJ, Tulkens PM, Spinewine A, Van Bambeke F. Development and validation of a high performance liquid chromatography assay for the determination of temocillin in serum of haemodialysis patients. J Pharm Biomed Anal. 2014 Mar;90:192-7. doi: 10.1016/j.jpba.2013.12.002. Epub 2013 Dec 12.
PubMed 24389461Miranda Bastos AC, Vandecasteele SJ, Spinewine A, Tulkens PM, Van Bambeke F. Temocillin dosing in haemodialysis patients based on population pharmacokinetics of total and unbound concentrations and Monte Carlo simulations. J Antimicrob Chemother. 2018 Jun 1;73(6):1630-1638. doi: 10.1093/jac/dky078.
PubMed 29579214
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Pharmacokinetic Study: Is Three Times Weekly Temocillin Appropriate for the Treatment of Severe Gram-negative Infections in Patients With ESRD Treated With Intermittent Hemodialysis?
- ClinicalTrials.gov ID
- NCT02285075
- Acronym / sponsor ID
- SVDC Temocillin 1
- Keywords
- temocillin, PD/PD, T>MIC
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- AZ Sint-Jan AVUniversity, hospital or other
- Collaborators
- Paul Tulkens, Louvain drug research institute, belgium, Francoise Van Bambeke, Louvain drug research institute, belgium, Ana Miranda Bastos, Louvain drug research institute, belgium
- Study start
- Jun 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 6 Nov 2014 (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.
The current study aimed to explore the pharmacokinetics of temocillin in patients treated with haemodialysis and to demonstrated whether or not the pharmacodynamics target of a time above a MIC of 16 mg/L of more than 40 and 60 % of the dosing interval could be obtained with a dosing schedule of 1 gram/24 hours, 2 gram/48 hours and 3 gram/72 hours, all of these doses given after haemodialysis sessions only.
Detailed description
Background: Temocillin is a renally cleared penicillin with long serum half-live and potent activity against most gram-negative bacteria, making it an ideal candidate for treatment given on dialysis days only of severe gram-negative infections in patients with ESRD treated with haemodialysis.
Endpoints:
Primary: The current study aimed to demonstrated by measurement of AUC whether or not the pharmacodynamics target of a time above a MIC of 8 and 16 mg/L of more than 40 and 60 % of the dosing interval could be obtained with a dosing schedule of 1 gram/24 hours, 2 gram/48 hours and 3 gram/72 hours, all of these doses given after haemodialysis sessions only.
Secondary: Key pharmacokinetic and dialytic parameters were determined as previously described16. The following parameters were recorded: the volume of distribution Vd (determined as Vd = dose / (Tempeak - Temtrough) in liter); the Vd/Wt (in liter/kg body weight); the non-dialysis clearance of temocillin (Ke(non-dialysis) = [ln(Tempeak) - ln(Tempre)] / time between peak level and start of next dialysis); the non-dialysis half-life (T1/2(non-dialysis) = 0.693 / Ke(non-dialysis) in hours); the dialysis clearance of temocillin (Ke(dialysis) = [ln(Tempre) - ln(Tempost)] / dialysis duration); the dialysis half-life (T1/2(dialysis) = 0.693 / Ke(dialysis) in hours); the Urea Reduction Ratio (URR = (BUNpre - BUNpost) / BUNpre); the Temocillin Reduction Ratio TRR = (Tempre - Tempost) / Tempre); the Temocillin Removal Ratio (the total amount of temocillin recovered in the dialysate, based on the area under the curve of the temocillin removal rate and the treatment time); and the AUC of temocillin. For all PK/PD analysis, the non-compartmental method using RStudio 0.98.501 with R 3.0.2 software was used.
Methods: Pharmacokinetic study measuring total and free temocillin concentrations in patients treated with intermittent haemodialysis and temocillin. Blood samples were drawn just before, and at 0.5, 3, 6, 12, 20 (before dialysis) and 24 (at the end of dialysis) hours after start of the infusion when patients were dialysed with a 1-day interval; just before and at 0.5, 3, 6, 12, 24, 36, 44 (before dialysis) and 48 (at the end of dialysis) hours after start of the infusion when patients were dialysed with a 2-day interval, and just before and at 0.5, 3, 6, 12, 24, 36, 48, 68 (before dialysis) and 72 (at the end of dialysis) hours after start of the infusion if patients were dialysed with a 3-day interval. Patients were followed for 1 to 6 subsequent AUC. Dialysate samples were taken 1, 2, 3 and 4 h after the start of dialysis. All samples were taken from an arterial or venous catheter, after thorough rinsing. Serum (obtained by centrifugation after blood clotting) and dialysate was frozen (-80 C) immediately after sampling until analysis.
Temocillin total and free concentrations were determined with high performance liquid chromotography(HPLC) with a LiChrospher 100 RP-18 5 μm column (Merck AG), using an elution buffer 100 mM Na acetate buffer pH 7/acetonitrile (95:5, v/v), a flow rate 1 mL/min and a Waters 2690 Alliance System (Waters Corp., Milford, MA, USA), with quantification at 235 nm as previously described.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| temocillin PK/PD in haemodialysis | Other | Drug: temocillin PK/PD in haemodialysisPharmacokinetic study measuring total and free temocillin concentrations in patients treated with haemodialysis receiving 1 gram temocillin for a 1 day interval, 2 gram temocillin for a two day interval and 3 gram temocillin for a 3 day interval to the next dialysis session |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- all patients under treatment with haemodialysis for ESRD for whom a treatment with temocillin was indicated according to the attending physician were eligible for the study.
Key exclusion criteria (5 listed)
- an age of less than 18 years
- an estimated life-expectance of < 24 hours due to major co-morbid conditions
- pregnancy
- an IgE-mediated allergy to penicillins
- patients not giving informed consent.
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 |
|---|---|---|
| temocillin PK/PD in haemodialysisPharmacokinetic study measuring total and free temocillin concentrations just before, and at 0.5, 3, 6, 12, 20 (before dialysis) and 24 (at the end of dialysis) hours after start of the infusion when patients were dialysed with a 1-day interval; just before and at 0.5, 3, 6, 12, 24, 36, 44 (before dialysis) and 48 (at the end of dialysis) hours after start of the infusion when patients were dialysed with a 2-day interval, and just before and at 0.5, 3, 6, 12, 24, 36, 48, 68 (before dialysis) and 72 (at the end of dialysis) hours after start of the infusion if patients were dialysed with a 3-day interval in order to determine basic PK and PD parameters in patients treated with intermittent haemodialysis and temocillin (Vd, T1/2, protein binding, clearance, reduction rate and T > MIC of 8 and 16 mg/L). | Drug | temocillin PK/PD in haemodialysis |
Primary outcome
% of the dosing interval time above an MIC of 8 and 16 mg/L (% T>MIC 8 or 16 mg/L)
Time frame: two to ten days
Is T > MIC 8 and 16 mg/ML > 40 or 60 %
6 secondary outcomes
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Time frame: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Time frame: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Time frame: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Time frame: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Time frame: two to ten days
Determine basic pharmacokinetic parameters of temocillin in intermittent haemodialysis
Time frame: two to ten days
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 5 Jan 2016.
- Results publication: PubMed 24389461Miranda Bastos AC, Vandecasteele SJ, Tulkens PM, Spinewine A, Van Bambeke F. Development and validation of a high performance liquid chromatography assay for the determination of temocillin in serum of haemodialysis patients. J Pharm Biomed Anal. 2014 Mar;90:192-7. doi: 10.1016/j.jpba.2013.12.002. Epub 2013 Dec 12.
- Derived from this study: PubMed 29579214Miranda Bastos AC, Vandecasteele SJ, Spinewine A, Tulkens PM, Van Bambeke F. Temocillin dosing in haemodialysis patients based on population pharmacokinetics of total and unbound concentrations and Monte Carlo simulations. J Antimicrob Chemother. 2018 Jun 1;73(6):1630-1638. doi: 10.1093/jac/dky078.
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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.
Stefaan J Vandecasteele, MD, PhD principal investigator
AZ Sint-Jan AV
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 temocillin PK/PD in haemodialysis in people with Gram-Negative Bacterial Infections and Renal Failure Chronic Requiring Hemodialysis, run by AZ Sint-Jan AV at 2 sites in Belgium.
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 1 inclusion and 5 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 5 Jan 2016. 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 Belgium. 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 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?
% of the dosing interval time above an MIC of 8 and 16 mg/L (% T>MIC 8 or 16 mg/L) (time frame: two to ten days). 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 NCT02285075, which also lists 2 linked publications.
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 5 Jan 2016.