A study of aerosol Amikacin and Fosfomycin delivered via a new nebulizer system in mechanically ventilated patients.
A randomised, double blind, placebo controlled, dose escalation study of aerosolized Amikacin and Fosfomycin delivered via the PARI investigational eFlow inline nebulizer system in mechanically ventilated patients.
Cardeas Pharma
9 participants
Jul 26, 2012
Interventional
Conditions
Summary
Ventilator Associated Tracheobronchitis (VAT) and Ventilator Associated Pneumonia (VAP) are common complications of mechanical ventilation, that may result in prolonging ICU stays and can also be fatal for critically ill patients. The standard treatment is currently intravenous antibiotics. The emergence of multidrug resistant bacteria and Gram negative pathogens makes this approach increasingly less effective. In order to improve treatment options, aerosol antibiotics have been investigated. They generally result in a higher sputum concentration compared to intravenous delivery, with reduced systemic exposure. Studies of aerosolized antibiotics to treat or to prevent VAP indicate benefits such as lower rates of VAP at the end of treatment, reduced usage of systemic antibiotics, and earlier weaning of patients from the ventilator, leading to shorter stays in the ICU. Since VAP may be caused by Gram negative and/or positive bacteria, an adequate antibiotic regimen needs to cover both, and also have coverage for MRSA. This study therefore plan to investigate the combination of amikacin and fosfomycin.
Eligibility
Inclusion Criteria3
- Clinical diagnosis of VAP or VAT and expected to be on mechanical ventilation for at least 3 days
- Gram positive or gram negative stain of the tracheal aspirate
- Able to produce 1ml of tracheal aspirate for PK analyses
Exclusion Criteria12
- Severely compromised or suppressed immune system prior to hospital admission
- Fraction of Inspired Oxygen (FIO2) > 0.8 at enrolment
- Relative hypoxemia (O2 saturation of less than 93% on an FIO2 =0.8) at enrolment
- PEEP > 15cm H2O at enrolment
- Creatinine > 0.18 mmol/L
- Positive pregnancy screening test or breast feeding (for female participants only)
- Burns to greater than 40% of the body
- Current treatment with systemic amikacin or fosfomycin within 48 hours of dosing
- A history of previous allergy or sensitivity to amikacin or fosfomycin
- Participation in a clinical study with administration of an investigational drug product within three months of Investigational Product administration.
- Blood hemoglobin < 70 g/L at enrolment.
- Any other condition which in the view of the Investigator is likely to interfere with the study or put the patient at risk.
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Interventions
Aerosolized Amikacin and Fosfomycin delivered via the PARI Investigational eFlow Nebulizer System. Amikacin/Fosfomycin (50mg/ml amikacin and 20mg/ml fosfomycin) will be supplied as a solution. Single dose escalating study with 3 doses adminitered over 3 days every 24hrs. Administration will take approx 15-30mins. Patients will sequentially fill 4 cohorts. Cohort 1 (no=3) will recive 2ml, 4ml and 6ml doses on days 1 2 and 3 respectively Cohort 2 (no =3) will recive 4ml, 6ml and 8ml doses on days 1 2 and 3 respectively Cohort 3 (no =3) will recive 6ml, 8ml and 10ml doses on days 1 2 and 3 respectively Cohort 4 (no=6) will recive 8ml, 10ml and 12ml doses on days 1 2 and 3 respectively. The eflow nebulizer system is based on eFlow technolgy. The eFlow is a single patient multiuse nebulizer that uses a vibrating perforated membrane to generate the aerosol. It will be positioned in the inspiratory tubing approx 15 cm from the Y-piece (between the Puritan Bennett 840 ventiator and the patient). Once in place the nebulizer will remain in line until all study drug doses have been delivered.
Locations(1)
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ACTRN12612000273886