None listed
Conditions
Brief summary
This research is testing different methods for how an antibiotic can be delivered intravenously (into a vein). In this case, intermittent administration of the antibiotic (20-30 minute infusion every 6-8 hours), is being compared with continuous delivery (over 24-hours). Treatment of infection in the intensive care unit (ICU) represents an ongoing challenge for doctors. Successful therapy relies on early recognition of infection, and the timely application of antibiotics. Antibiotic dosing (how much and how often we give the drug) should aim to rapidly achieve adequate antibiotic levels through out the body. This is in order to ensure the causative pathogen (the ‘bug’ causing the infection), is eradicated quickly. This tends to be more difficult in ICU patients due to their underlying illness, and the requirement for other therapies (such as breathing support machines, ‘fluid drips’, and surgical procedures). The optimum method of delivering antibiotics is unknown, and current dosing strategies are generally based on those used outside the ICU, where patients are not as sick. Previous research has shown that trauma patients admitted to the ICU are at high risk of developing hospital-acquired infections. Unfortunately, these can often negatively impact patient outcomes (such as length of stay in hospital). Achieving better antibiotic levels in the body, by using alternative dosing strategies, may be one way to improve these outcomes. This is particularly the case for trauma patients being cared for in the ICU, where we know that antibiotic prescription is more difficult. However, before simply changing prescribing habits, we need to measure how effective these new dosing methods are, in comparison to what is done routinely. The purpose of this research is therefore to test a new method of administering the antibiotic piperacillin-tazobactam, which will hopefully result in better levels of the drug in the bloodstream. An ICU patient is eligible to be involved in this project, because they have suffered trauma, and their doctor has prescribed this drug, as they believe your the patient has an infection.
Interventions
Please refer to Appendix A table in attachment 1 on ANZCTR record.
Following randomisation, study participants will receive either standard prescription piperacillin-tazobactam, or augmented dosing, based on an ‘ARC Dose Optimisation Protocol’ . APPENDIX A-Protocol
An 8-hr urinary creatinine clearance measured on Day 1, and then every alternate day post randomisation, will be used to optimise therapy in those patients randomised to the augmented dosing strategy. The total duration of therapy w
Please refer to Appendix A table in attachment 1 on ANZCTR record. Following randomisation, study participants will receive either standard prescription piperacillin-tazobactam, or augmented dosing, based on an ‘ARC Dose Optimisation Protocol’ . APPENDIX A-Protocol An 8-hr urinary creatinine clearance measured on Day 1, and then every alternate day post randomisation, will be used to optimise therapy in those patients randomised to the augmented dosing strategy. The total duration of therapy will be at the discretion of the treating clinician, although augmented dosing will cease on Day 7, or discharge from the ICU. In those randomised to standard prescription, this will utilise the current dosing strategies routinely employed at each participating institution. This typically involves intermittent administration of 4.5g IV piperacillin-tazobactam every 6 to 8 hours. Optimisation of dosing on the basis of CLCR measurements is not routinely performed at either site. Those patients randomised to the ARC Dose Optimisation protocol (See appendix 1) will commence a continuous infusion (over a 24 hour period) of their currently prescribed dose. That is, if a patient is prescribed 4.5g IV piperacillin-tazobactam every 6 hours, a bag of 250mls 0.9% Sodium Chloride will be prepared with 4 doses of 4.5g IV piperacillin-tazobactam to be administered continuously. All patients randomised to the ARC protocol will receive the total daily antibiotic dose delivered over 24hrs in a 250ml bag of Sodium Chloride 0.9%. Standard care dosing is to be delivered as per each units usual drug dosing policy. Dosing is dependent on the clinicians prescription for the first study dosing period.
Sponsors
The Univerity of Queensland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Any patient admitted to the ICU post multi-trauma, receiving piperacillin-tazobactam for presumed or confirmed infection. Inclusion Criteria: 1. Age greater than or equal to 18 and less than or equal to 50 years 2. Admission post trauma 3. Informed consent is obtained from the patient or surrogate decision maker 4. The patient is anticipated to require ICU care beyond the next calendar day 5. Plasma creatinine concentration < 100 micromol/L on the day of randomisation 6. Presence of an indwelling urinary catheter (IDC)
Exclusion criteria
Exclusion criteria: 1. Evidence of acute kidney injury – as per the RIFLE criteria 2. Evidence of acute liver injury – defined as an AST or ALT > 5 x upper limit of normal (ULN), or AST or ALT > 3 x ULN with associated total bilirubin > 2 x ULN 3. Evidence of active haemorrhage – defined by a fall in haemoglobin concentration > 20g/L or the need for > 2 units RBC in the preceding 24hrs 4. Increased risk of bleeding – defined by a platelet count < 50, INR or aPTT > 2 x ULN 5. Extremes of body size – defined as a body mass index (BMI) < 16 or greater than and equal to 40 kg/m2 6. Pregnancy 7. Treatment intent is palliative 8. Death is deemed imminent and inevitable 9. Known hypersensitivity to piperacillin-tazobactam 10. Has received piperacillin-tazobactam therapy for > 24hrs prior to randomisation 11. Not eligible for Medicare
Outcome results
None listed