Trial Outcomes & Findings for Pharmacokinetics of Piperacillin, Given as Continuous Infusion to Patients With Cystic Fibrosis (NCT NCT01983787)
NCT ID: NCT01983787
Last Updated: 2015-12-11
Results Overview
The free, non-protein bound fraction of plasma piperacillin for each patient was determined using Ultra High Performance Liquid Chromatography. The concentration was compared to the MIC-value (Minimal Inhibitory Concentration) of the pathogen isolated in a sputum sample collected prior to initiation of antibiotic treatment. Infusion pumps with 16 g of piperacillin per 24 hours were initially used and five patients had piperacillin plasma-concentrations monitored during this treatment regimen. However, in three of these patients, the piperacillin plasma concentrations were unexpectedly low and dropped to a level below the MIC. This was found to be due to antibiotic crystallization within the infusion pumps as a result of the antibiotic concentration being too high. Consequently, infusion pumps with 12 g of piperacillin per 24 hours were used in stead. The median piperaillin concentrations reported below are derived from all measurements within the two weeks of treatment.
Recruitment status
COMPLETED
Target enrollment
10 participants
Primary outcome timeframe
Piperacillin plasma-concentration was determined 3-5 times for each patient, during the 2 weeks of piperacillin treatment
Results posted on
2015-12-11
Participant Flow
Participant milestones
| Measure |
Pharmacokinetics Piperacillin
Patients with cystic fibrosis with pulmonary exacerbation, treated with Piperacillin/Tazobactam, given as continuous infusion for a period of two weeks.
|
|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
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10
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics of Piperacillin, Given as Continuous Infusion to Patients With Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Pharmacokinetics Piperacillin
n=10 Participants
Patients with cystic fibrosis and pulmonary exacerbation, treated with Piperacillin/Tazobactam, given as continuous infusion for a period of two weeks.
|
|---|---|
|
Age, Categorical
<=18 years
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0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
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10 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
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0 Participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Piperacillin plasma-concentration was determined 3-5 times for each patient, during the 2 weeks of piperacillin treatmentThe free, non-protein bound fraction of plasma piperacillin for each patient was determined using Ultra High Performance Liquid Chromatography. The concentration was compared to the MIC-value (Minimal Inhibitory Concentration) of the pathogen isolated in a sputum sample collected prior to initiation of antibiotic treatment. Infusion pumps with 16 g of piperacillin per 24 hours were initially used and five patients had piperacillin plasma-concentrations monitored during this treatment regimen. However, in three of these patients, the piperacillin plasma concentrations were unexpectedly low and dropped to a level below the MIC. This was found to be due to antibiotic crystallization within the infusion pumps as a result of the antibiotic concentration being too high. Consequently, infusion pumps with 12 g of piperacillin per 24 hours were used in stead. The median piperaillin concentrations reported below are derived from all measurements within the two weeks of treatment.
Outcome measures
| Measure |
Pharmacokinetics Piperacillin 16g/Day
n=5 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks.
|
Pharmacokinetics Piperacillin 12g/Day
n=5 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.
|
T>MIC 16g/Day, Patient 3
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Pseudomonas aeruginosa. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 16g/Day, Patient 4
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC12g/Day, Patient 6
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 7
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 8
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 9
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Acromobacter. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 10
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
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|---|---|---|---|---|---|---|---|---|---|
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Blood-plasma Concentration of Piperacillin
|
21 mg/L
Interval 5.0 to 33.5
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21 mg/L
Interval 15.0 to 42.0
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—
|
—
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—
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—
|
—
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—
|
—
|
SECONDARY outcome
Timeframe: Patients will be followed for the duration of treatment, which is approximately 2 weeks.The time, expressed in percentage, for which the plasma concentration of Piperacillin lies above the minimum inhibitory concentration for the pathogen,during the treatment. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%. MIC for the pathogen in sputum was not reported in patient 5. Therefore,T\>MIC for this patient could not be estimated. Patient 1-5 were treated with piperacillin 16g/day. Patient 6-10 were treated with piperacillin 12g/day.
Outcome measures
| Measure |
Pharmacokinetics Piperacillin 16g/Day
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks.
|
Pharmacokinetics Piperacillin 12g/Day
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.
|
T>MIC 16g/Day, Patient 3
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Pseudomonas aeruginosa. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 16g/Day, Patient 4
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC12g/Day, Patient 6
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 7
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 8
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 9
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Acromobacter. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 10
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
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|---|---|---|---|---|---|---|---|---|---|
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The Time Above the Minimum Inhibitory Concentration (T>MIC)
|
100 % of time above the MIC
|
100 % of time above the MIC
|
75 % of time above the MIC
|
75 % of time above the MIC
|
100 % of time above the MIC
|
100 % of time above the MIC
|
100 % of time above the MIC
|
100 % of time above the MIC
|
100 % of time above the MIC
|
SECONDARY outcome
Timeframe: Sputum sample was collected 3 to 7 days before treatment initiation.MIC to piperacillin/tazobactam was obtained by using E-tests (AB Biodisk, Solna, Sweden) on Mueller-Hinton agar plates incubated at 35 ± 2 degrees Celcius with inoculum, incubation time and atmosphere in accordance to the E-test application guide.
Outcome measures
| Measure |
Pharmacokinetics Piperacillin 16g/Day
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks.
|
Pharmacokinetics Piperacillin 12g/Day
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.
|
T>MIC 16g/Day, Patient 3
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Pseudomonas aeruginosa. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 16g/Day, Patient 4
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC12g/Day, Patient 6
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 7
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 8
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 9
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Acromobacter. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
|
T>MIC 12g/Day, Patient 10
n=1 Participants
Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 12 g/24 hours, given as continuous infusion for a period of two weeks.Patients with cystic fibrosis , treated with Piperacillin/Tazobactam 16 g/24 hours, given as continuous infusion for a period of two weeks. Pathogen in sputum: Staphylococcus aureus. If the piperacillin concentration at all measurements during the treatment period was at a level above the MIC, T\>MIC is reported as 100%.
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|---|---|---|---|---|---|---|---|---|---|
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MIC of Pathogen Detected in Sputum Sample, Prior to Initiation of Treatment.
|
3 mg/L
|
8 mg/L
|
16 mg/L
|
3 mg/L
|
0.5 mg/L
|
3 mg/L
|
3 mg/L
|
0.75 mg/L
|
2 mg/L
|
Adverse Events
Pharmacokinetics Piperacillin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Kristina Öbrink-Hansen
Aarhus University Hospital, Department of infectious diseases
Phone: +4578452845
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place