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Trial registered on ANZCTR


Registration number
ACTRN12612000273886
Ethics application status
Approved
Date submitted
6/03/2012
Date registered
7/03/2012
Date last updated
9/12/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of aerosol Amikacin and Fosfomycin delivered via a new nebulizer system in mechanically ventilated patients.
Scientific title
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.
Secondary ID [1] 280082 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ventilator Associated Pneumonia (VAP) 285990 0
Ventilator Associated Tracheobronchitis (VAT) 285991 0
Condition category
Condition code
Respiratory 286179 286179 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 284404 0
Treatment: Drugs
Intervention code [2] 284405 0
Treatment: Devices
Comparator / control treatment
The Placebo is 0.9% saline. On day 3 only, each patient will recieve a volume matched dose of placebo in addition to the investigation drug delivered via the Pari eFlow nebulizer ie all patients will recieve investigational drug on days 1 and 2 at the required dosage but on day 3 patients will receive investigation drug and placebo (2hrs apart). The day 3 dose of the investigation drug will be the same volume amount as for the intervention group on day 3 but will be given 2hrs apart
Control group
Placebo

Outcomes
Primary outcome [1] 286647 0
Plasma PK amikacin/fosfomycin concentrations following 2ml, 4ml, 6ml, 8ml, 10ml and 12ml dosing of nebulised amikacin/fosfomycin
Timepoint [1] 286647 0
blood samples at pre dose, 10mins, 1hr, 2hr, 4hr, 6hr and 24hr post dose
Primary outcome [2] 286648 0
Tracheal aspirate amikacin/fosfomycin concentrations following 2ml, 4ml, 6ml, 8ml, 10ml and 12ml dosing of nebulised amikacin/fosfomycin
Timepoint [2] 286648 0
Tracheal aspirate samples at pre dose, 15mins, 1hr, 2hr, 4hr, 6hr and 24hr post dose
Secondary outcome [1] 296372 0
To evaluate the safety and tolerability of nebulised amikacin/fosfomycin
Timepoint [1] 296372 0
ongoing through study until 24 hrs post dose 3.

The following will be ultilised- physical exam, vital signs (incl Heart rate, rsp rate, Blood pressure and temp) Heamatology, serum biochemistry, Urinalysis, Oximetry and peak and plateau airway pressures.

Adverse events and SAEs will also be monitored by the PI from screening visit until 24 hours post dose 3. As this is a phase 1 study, adverse events and SAEs are unknown but will be recorded if/as they occur.
Secondary outcome [2] 296373 0
To evaluate doses of amikacin/fosfomycin for future studies
Timepoint [2] 296373 0
Ongoing through study until 24 hrs post dose 3. Final evaluation will not occur until all data is collected and analysed for Clinical Study Report.

Eligibility
Key inclusion criteria
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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severely compromised or suppressed immune system prior to hospital admission
2. Fraction of Inspired Oxygen (FIO2) > 0.8 at enrolment
3. Relative hypoxemia (O2 saturation of less than 93% on an FIO2 =0.8) at enrolment
4. PEEP > 15cm H2O at enrolment
5. Creatinine > 0.18 mmol/L
6. Positive pregnancy screening test or breast feeding (for female participants only)
7. Burns to greater than 40% of the body
8. Current treatment with systemic amikacin or fosfomycin within 48 hours of dosing
9. A history of previous allergy or sensitivity to amikacin or fosfomycin
10. Participation in a clinical study with administration of an investigational drug product within three months of Investigational Product administration.
11. Blood hemoglobin < 70 g/L at enrolment.
12. Any other condition which in the view of the Investigator is likely to interfere with the study or put the patient at risk.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
26/07/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
9
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 6959 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 284833 0
Commercial sector/Industry
Name [1] 284833 0
Cardeas Pharma
Country [1] 284833 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Cardeas Pharma
Address
2025 First Avenue, Suite 1200 Seattle WA9121
Country
United States of America
Secondary sponsor category [1] 283711 0
Commercial sector/Industry
Name [1] 283711 0
INCResearch
Address [1] 283711 0
124 Lipson St Port Adelaide SA 5015
Country [1] 283711 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286823 0
Ethics committee address [1] 286823 0
Ethics committee country [1] 286823 0
Date submitted for ethics approval [1] 286823 0
19/03/2012
Approval date [1] 286823 0
Ethics approval number [1] 286823 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33872 0
Dr Tim Leong
Address 33872 0
Alfred Hospital, ICU Dept, Commercial Rd, Melbourne 3004 VIC
Country 33872 0
Australia
Phone 33872 0
61 3 9076 2000
Fax 33872 0
Email 33872 0
T.Leong@alfred.org.au
Contact person for public queries
Name 17119 0
Tammy Abuan
Address 17119 0
2025 First Avenue, Suite 1200 Seattle WA 98121
Country 17119 0
United States of America
Phone 17119 0
206-973-1026
Fax 17119 0
Email 17119 0
tammy.abuan@cardeaspharma.com
Contact person for scientific queries
Name 8047 0
Tammy Abuan
Address 8047 0
2025 First Avenue, Suite 1200 Seattle WA 98121
Country 8047 0
United States of America
Phone 8047 0
206-973-1026
Fax 8047 0
Email 8047 0
tammy.abuan@cardeaspharma.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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