Clinical Trial Results:
Pharmacokinetics of small spectcrum beta-lactam antibiotics (Amoxicillin/Clavulanic Acid and Cefuroxime) on intensive care.
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Summary
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EudraCT number |
2011-006107-35 |
Trial protocol |
BE |
Global end of trial date |
21 Jan 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Jul 2021
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First version publication date |
01 Jul 2021
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Other versions |
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Summary report(s) |
Antimicrob Chemother 2013 Antimicrob Chemother 2014 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AGO/2011/012
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01581047 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ghent University Hospita
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Sponsor organisation address |
Corneel Heymanslaan 10, Ghent, Belgium, 9000
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Public contact |
Trial Bureau, Ghent University Hospital, 32 93320500, Trialbureau@uzgent.be
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Scientific contact |
Trial Bureau, Ghent University Hospital, 32 93320500, Trialbureau@uzgent.be
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 May 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Jan 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate the pharmacokinetics of Amoxicillin/Clavulanic acid and Cefuroxime antibiotics in patients hospitalized in the ntensive care.
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Protection of trial subjects |
Ethics review and approval, informed consent, supportive care and routine monitoring.
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Background therapy |
Adequate antibiotic therapy is very important in the treatment of infections. Spectrum and dosing of the antibiotics are two factors of the therapy: the spectrum of an antibiotic can't be changed, but the dosing scheme can be optimized. Recent studies proved that an optimized dosing scheme can improve the efficacy of the treatment. Broad-spectrum antibiotics have unpredictable pharmacokinetics in patients on intensive care units. This is due to the pathophysiologic processes in the patients on intensive care units: increased distribution volume, hypoproteinemia, organ failure… The investigators guess that similar processes influence the pharmacokinetics of small spectrum antibiotics (like amoxicillin and cefuroxime), but data lacks. Because the pharmacokinetics of broad spectrum antibiotics in seriously ill patients are better known, physicians are more confident prescribing these drugs. Studying the pharmacokinetic interactions of small spectrum antibiotics in seriously ill patients, can help to give the physician the confidence to prescribe these small-spectrum antibiotics. | ||
Evidence for comparator |
In this study, the investigators will study the pharmacokinetics of amoxicillin/clavulanic acid and cefuroxime, in 60 patients on intensive care. 8 blood samples will be drawn via a central catheter on different moments after one administration of the antibiotic in the steady state phase. All the patients are prescribed the antibiotics for the treatment of their infections: they get the antibiotic therapy anyway. By measuring the concentrations on different moments after one administration, the investigators can reconstruct the pharmacokinetic function. | ||
Actual start date of recruitment |
15 Mar 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 37
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Worldwide total number of subjects |
37
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EEA total number of subjects |
37
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
22
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From 65 to 84 years |
14
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85 years and over |
1
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Recruitment
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Recruitment details |
59 patients were screened in the period from 15-Mar-2012 till 21-Jan-2014. 37 patients were included and completed the trial. End of trial notification was dated 21-Jan-2014 (last patient last visit) and submitted to EC and CA 02-Jun-2014 | |||||||||
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Pre-assignment
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Screening details |
Male/Female >18 Years Patients on the intensive care , who are treated with amoxicillin/clavulanic acid or cefuroxime for an infection Exclusion Criteria: informed consent lacking haematocrit < 21 % arterial catheter lacking | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Amoxicillin/Clavulanic Acid | |||||||||
Arm description |
Patients in the intensive care unit, with an infection which will be treated with Amoxicillin/Clavulanic Acid. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Amoxicillin/Clavulanic Acid
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Investigational medicinal product code |
J01CR02
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
1 g 4 x/day
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Arm title
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Cefuroxime | |||||||||
Arm description |
Patients in the intensive care unit, with an infection which will be treated with Cefuroxime. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Cefuroxime
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Investigational medicinal product code |
J01D A06
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Solution for infusion
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Dosage and administration details |
1,5 g 3 x/dag
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Area under the serum concentration versus time curve (AUC)
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Area under the serum concentration versus time curve (AUC) of Amoxicillin/Clavulanic acid. The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC). [Time Frame: Before and at 15, 30, 45, 60, 120, 240 and 360 minutes after administration]
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Subject analysis set title |
Area under the serum concentration versus time curve (AUC)
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Area under the serum concentration versus time curve (AUC) of Cefuroxime. The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC). [Time Frame: Before and at 15, 30, 45, 60, 120, 240 and 480 minutes after administration]
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End points reporting groups
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Reporting group title |
Amoxicillin/Clavulanic Acid
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Reporting group description |
Patients in the intensive care unit, with an infection which will be treated with Amoxicillin/Clavulanic Acid. | ||
Reporting group title |
Cefuroxime
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Reporting group description |
Patients in the intensive care unit, with an infection which will be treated with Cefuroxime. | ||
Subject analysis set title |
Area under the serum concentration versus time curve (AUC)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Area under the serum concentration versus time curve (AUC) of Amoxicillin/Clavulanic acid. The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC). [Time Frame: Before and at 15, 30, 45, 60, 120, 240 and 360 minutes after administration]
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Subject analysis set title |
Area under the serum concentration versus time curve (AUC)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Area under the serum concentration versus time curve (AUC) of Cefuroxime. The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC). [Time Frame: Before and at 15, 30, 45, 60, 120, 240 and 480 minutes after administration]
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End point title |
Area under the serum concentration versus time curve (AUC) [1] | ||||||||||||
End point description |
The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC).
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End point type |
Primary
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End point timeframe |
Time Frame: Before and at 15, 30, 45, 60, 120, 240 and 360 minutes after administration Amoxicillin/Clavulanic acid
Time Frame: Before and at 15, 30, 45, 60, 120, 240 and 480 minutes after administration Cefuroxime
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis available |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Overall study
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||
Dictionary version |
5
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| Frequency threshold for reporting non-serious adverse events: 0.05% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No non-serious adverse events were recorded for the participating patients |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
