Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01667094




Registration number
NCT01667094
Ethics application status
Date submitted
13/08/2012
Date registered
17/08/2012
Date last updated
20/04/2017

Titles & IDs
Public title
A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
Scientific title
Continuous-infusion Anti-pseudomonal ß-lactams for the Treatment of Acute, Infective Pulmonary Exacerbations in Cystic Fibrosis
Secondary ID [1] 0 0
U1111-1132-8291
Secondary ID [2] 0 0
249/12
Universal Trial Number (UTN)
Trial acronym
CISTIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Intermittent, short infusion Ceftazidime
Treatment: Drugs - Continuous infusion Ceftazidime
Treatment: Drugs - Intermittent, short infusion Meropenem
Treatment: Drugs - Continuous infusion Meropenem
Treatment: Drugs - Intermittent, short infusion Ticarcillin-clavulanate
Treatment: Drugs - Continuous infusion Ticarcillin-clavulanate
Treatment: Drugs - Intermittent, short infusion Cefepime
Treatment: Drugs - Continuous infusion Cefepime
Treatment: Drugs - Continuous infusion Piperacillin tazobactam
Treatment: Drugs - Intermittent, short infusion Piperacillin tazobactam

Active Comparator: Intermittent, short infusion - Infusion over 30 minutes of either:
Cefepime 1g q8/24 OR Ceftazidime 2g q8/24 OR Meropenem 1g q8/24 OR Piperacillin-Tazobactam 4.5g q8/24 OR Ticarcillin-clavulanate 3.1g q6/24
Antibiotic chosen by treating physician

Experimental: Continuous infusion - Continuous infusion of either:
Cefepime 1.5g over 12h, q12/24 after initial loading dose of 500mg OR Ceftazidime 3g over 12h, q12/24 after initial loading dose 1g OR Meropenem 1.5g over 12h, q12/24 after initial loading dose 500mg OR Piperacillin-tazobactam 13.5g over 24h after initial loading dose 2.25g OR Ticarcillin-clavulanate 12.4g over 24h after initial loading dose 1.55g
Antibiotic chosen by treating physician


Treatment: Drugs: Intermittent, short infusion Ceftazidime
Ceftazidime 1g q8/24

Treatment: Drugs: Continuous infusion Ceftazidime
Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24

Treatment: Drugs: Intermittent, short infusion Meropenem
Meropenem 1g q8/24, infusion over 30 minutes

Treatment: Drugs: Continuous infusion Meropenem
Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24

Treatment: Drugs: Intermittent, short infusion Ticarcillin-clavulanate
Ticarcillin/clavulanate 3.1g q6/24

Treatment: Drugs: Continuous infusion Ticarcillin-clavulanate
Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24

Treatment: Drugs: Intermittent, short infusion Cefepime
Cefepime 1g q8/24

Treatment: Drugs: Continuous infusion Cefepime
Cefepime loading dose 500mg followed by 1.5g infused over 12/24, q12/24

Treatment: Drugs: Continuous infusion Piperacillin tazobactam
Piperacillin tazobactam loading dose of 4.5g infused over 30 minutes followed by 18g infused over 24/24, q24/24

Treatment: Drugs: Intermittent, short infusion Piperacillin tazobactam
Piperacillin tazobactam 4.5g q6/24
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score
Timepoint [1] 0 0
Day 0 to Day 14
Secondary outcome [1] 0 0
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score
Timepoint [1] 0 0
Day 0 to Day 7, Day 0 to Day 28
Secondary outcome [2] 0 0
Lung function testing; Forced volume expired in one second (FEV1)
Timepoint [2] 0 0
Day 0 to Day 7, Day 0 to Day 28
Secondary outcome [3] 0 0
C-reactive peptide (CRP)
Timepoint [3] 0 0
Day 0 to Day 3
Secondary outcome [4] 0 0
Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)
Timepoint [4] 0 0
Day 0 to Day 3, Day 0 to Day 7
Secondary outcome [5] 0 0
Time above minimum inhibitory concentration (MIC)
Timepoint [5] 0 0
Day 3
Secondary outcome [6] 0 0
Antibiotic stability
Timepoint [6] 0 0
Day 3
Secondary outcome [7] 0 0
Pseudomonas aeruginosa virulence gene determinants
Timepoint [7] 0 0
Day 0 to Day 3 and Day 0 to Day 7

Eligibility
Key inclusion criteria
1. Patients >= 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 of 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. concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory
failure,

4. impaired renal function with an estimated creatinine clearance < 60 mls/min,

5. patients allergic to ß-lactam antibiotics,

6. aminoglycoside contra-indicated,

7. intravenous antibiotics in the last 2 weeks, prior to this admission,

8. received more than 24 hours of intravenous antibiotics in this admission,

9. previous lung transplantation,

10. pregnancy or lactation, or

11. 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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2017
Actual
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3181 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
The Alfred
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Cystic fibrosis (CF) is an inherited disorder which results in increased thickness of
secretions, especially in the lungs. By adulthood, the majority of patients with CF will have
a bacteria living in their lungs, called Pseudomonas aeruginosa which can cause lung
infections. This usually results in worsening respiratory symptoms and often an acute
deterioration in their lung function. They are usually treated with antibiotics that target
the Pseudomonas aeruginosa. These antibiotics are typically given as short intravenous
infusions several times a day. This study aims to compare the standard method of giving these
antibiotics with a different strategy of giving these antibiotics to see if this can improve
the outcomes of treatment of these infections and reduce the amount of Pseudomonas aeruginosa
in the lungs of these patients. This strategy consists of giving the same antibiotics
continuously, to ensure there is always enough antibiotic in the bloodstream and the lung to
be able to kill the bacteria.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01667094
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anton Peleg, MBBS, FRACP.
Address 0 0
The Alfred
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01667094