Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000945820
Ethics application status
Approved
Date submitted
13/08/2012
Date registered
4/09/2012
Date last updated
7/04/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Continuous infusion antipseudomonal
beta-lactams for acute infective exacerbations in cystic fibrosis: a prospective randomised controlled trial
Scientific title
Continuous infusion antipseudomonal
betalactams versus standard short infusions in the treatment of acute infective exacerbations in patients with cystic fibrosis - impact on clinical and microbiological outcomes
Secondary ID [1] 281016 0
Clinicaltrials.gov identifier NCT01667094
Universal Trial Number (UTN)
U1111-1132-8291
Trial acronym
CISTIC (Continuous Infusion Strategy To Improve Clinical outcomes)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute pulmonary exacerbation of cystic fibrosis 286950 0
Condition category
Condition code
Infection 287288 287288 0 0
Studies of infection and infectious agents
Respiratory 287492 287492 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 287661 287661 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Continuous infusion antipseudomonal beta-lactam. The antipseudomonal beta-lactam will be chosen by the treating physician and the method of administration will be subject to randomisation. Participants will receive ONE of the following intravenous antibiotics, as decided by their treating physician. Ceftazidime: Loading dose 500mg on day 1 then 3g infused over 24 hours continuously or Ticarcillin-clavulanate: Loading dose 1.5g ticarcillin/0.05g clavulanate on day 1 then 12g ticarcillin/0.4g clavulanate infused over 24 hours continuously or Meropenem: Loading dose 500mg on day 1 then 3g infused over 24 hours continuously or Cefepime: Loading dose 500mg on day 1 then 3g infused over 24 hours continuously or Piperacillin-tazobactam: Loading dose 2g piperacillin/0.25g tazobactam on day 1 then 16g piperacillin/2g tazobactam infused over 24 hours continously 24 hour infusions are repeated daily over the 14 day treatment period, i.e. continuous infusion for 14 days.
Intervention code [1] 285313 0
Treatment: Drugs
Comparator / control treatment
Intermittent, short (30 minute) infusion antipseudomonal beta-lactam Participants will receive ONE of the following intravenous antibiotics as decided by their treating physician: Ceftazidime: 2g every 8 hours or Ticarcillin-clavulanate: 3g ticarcillin/0.1g clavulanate every 6 hours or Meropenem: 1g every 8 hours or Cefepime: 1g every 8 hours or Piperacillin-tazobactam: 4g piperacillin/ 0.5g tazobactam every 6 hours Each infusion will be over 30 minutes. Total duration of treatment 14 days.
Control group
Active

Outcomes
Primary outcome [1] 287740 0
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score
Timepoint [1] 287740 0
Day 0 to Day 14
Secondary outcome [1] 298746 0
Change in lung function testing; Forced volume expired in one second (FEV1)
Timepoint [1] 298746 0
Day 0 to Day 7, Day 0 to Day 28
Secondary outcome [2] 298747 0
Change in C-reactive peptide (CRP) measured by blood analysis.
Timepoint [2] 298747 0
Day 0 to Day 3
Secondary outcome [3] 298748 0
Time to next infective exacerbation; measured from medical records data.
Timepoint [3] 298748 0
Within 12 months
Secondary outcome [4] 298749 0
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score
Timepoint [4] 298749 0
Day 0 to Day 7, Day 0 to Day 28
Secondary outcome [5] 298750 0
Quantitative bacterial load in sputum and virulence gene expression.
Quantitative PCR and RNA analysis on sputum samples
Timepoint [5] 298750 0
Day 0 to Day 3, Day 0 to Day 7
Secondary outcome [6] 298751 0
Time above minimum inhibitory concentration (MIC).
Substudy; if Pseudomonas aeruginosa isolated from participant's sputum, the MIC will be determined for the selected antibiotic. Blood samples will be taken to measure the antibiotic levels and a calculation of the time above minimum inhibitory concentration will be made from these measurements.
Timepoint [6] 298751 0
Day 3
Secondary outcome [7] 298752 0
Antibiotic stability data.
Samples will be taken from the infusion bag and the amount of antibiotic will be measured.
Timepoint [7] 298752 0
Day 3

Eligibility
Key inclusion criteria
1) Patients greater than or equal to 18 years of age,
2) Pseudomonas aeruginosa isolated in sputum within the last 12 months,
3) has an acute infective exacerbation, defined by international standards 2 or more of the following in the last 2 weeks:
change sputum volume or colour,
increased cough,
increased dyspnoea,
increased malaise, fatigue or lethargy,
anorexia or weight loss,
decrease in pulmonary function by 10% or more, or
new radiographic changes
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) patients < 18 yrs of age,
2) patients that do not meet the criteria for an acute infective exacerbation,
3) previous enrolment in the study,
4) concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory failure,
5) impaired renal function with an estimated creatinine clearance < 60 mls/min,
6) patients allergic to beta-lactam antibiotics,
7) aminoglycoside contra-indicated,
8) intravenous antibiotics in the last 2 weeks, prior to this admission,
9) received more than 24 hours of intravenous antibiotics in this admission,
10) previous lung transplantation,
11) pregnancy or lactation, or
12) inability to consent.

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)
Those patients who meet the inclusion criteria definition for a pulmonary exacerbation and admitted for intravenous antibiotics will be identified and consent sought.
The antipseudomonal beta-lactam will be chosen by the treating physician and the method of administration will be subject to randomisation.
Treatment allocation encoded by random numbers will be enclosed in numbered, sealed opaque envelopes which will be opened at the time of the subject commencing the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random numbers sequences will be generated by a computer program (STATA-11) in a block design by a study investigator not involved with recruitment.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/09/2012
Actual
26/11/2012
Date of last participant enrolment
Anticipated
31/01/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285805 0
Charities/Societies/Foundations
Name [1] 285805 0
Sylvia & Charles Viertel Charitable Foundation Clinical Investigatorship Award
Country [1] 285805 0
Australia
Primary sponsor type
Individual
Name
Dr Anton Peleg
Address
Department of Infectious Diseases
Level 2 Burnett Institute
The Alfred Hospital
PO Box 315
Praharn
VIC 3181
Country
Australia
Secondary sponsor category [1] 284630 0
None
Name [1] 284630 0
Address [1] 284630 0
Country [1] 284630 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287820 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 287820 0
Ethics committee country [1] 287820 0
Australia
Date submitted for ethics approval [1] 287820 0
06/06/2012
Approval date [1] 287820 0
16/07/2012
Ethics approval number [1] 287820 0
1/12/0249

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

Contacts
Principal investigator
Name 34461 0
Dr Anton Peleg
Address 34461 0
Department of Infectious Diseases, The Alfred Hospital Level 2 Burnett Institute PO Box 3181 Praharn VIC 3181
Country 34461 0
Australia
Phone 34461 0
613 9076 5436
Fax 34461 0
Email 34461 0
[email protected]
Contact person for public queries
Name 17708 0
Dr Katherine Langan
Address 17708 0
Department of Infectious Diseases, The Alfred Hospital
Level 2 Burnett Institute
PO Box 3181
Praharn
VIC 3181
Country 17708 0
Australia
Phone 17708 0
613 9076 5436
Fax 17708 0
613 9076 6557
Email 17708 0
[email protected]
Contact person for scientific queries
Name 8636 0
Dr Anton Peleg
Address 8636 0
Department of Infectious Diseases, The Alfred Hospital
Level 2 Burnett Institute
PO Box 3181
Praharn
VIC 3181
Country 8636 0
Australia
Phone 8636 0
613 9076 5436
Fax 8636 0
613 9076 6557
Email 8636 0
[email protected]

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.