Back to resultsA Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis (CISTIC)
Primary Purpose
Cystic Fibrosis
Status
Unknown status
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
Intermittent, short infusion Ceftazidime
Continuous infusion Ceftazidime
Intermittent, short infusion Meropenem
Continuous infusion Meropenem
Intermittent, short infusion Ticarcillin-clavulanate
Continuous infusion Ticarcillin-clavulanate
Intermittent, short infusion Cefepime
Continuous infusion Cefepime
Continuous infusion Piperacillin tazobactam
Intermittent, short infusion Piperacillin tazobactam
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring Pulmonary exacerbation, Continuous infusion, Antipseudomonal beta-lactams
Eligibility Criteria
Inclusion Criteria:
- Patients >= 18 years of age,
- Pseudomonas aeruginosa isolated in sputum within the last 12 months,
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
Exclusion Criteria:
- patients < 18 yrs of age,
- patients that do not meet the criteria for an acute infective exacerbation,
- concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory failure,
- impaired renal function with an estimated creatinine clearance < 60 mls/min,
- patients allergic to ß-lactam antibiotics,
- aminoglycoside contra-indicated,
- intravenous antibiotics in the last 2 weeks, prior to this admission,
- received more than 24 hours of intravenous antibiotics in this admission,
- previous lung transplantation,
- pregnancy or lactation, or
- inability to consent.
Sites / Locations
- The Alfred Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Intermittent, short infusion
Continuous infusion
Arm Description
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
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
Outcomes
Primary Outcome Measures
Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score
Secondary Outcome Measures
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score
Lung function testing; Forced volume expired in one second (FEV1)
C-reactive peptide (CRP)
Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)
Measured by PCR.
Time above minimum inhibitory concentration (MIC)
Antibiotic stability
For ceftazidime and meropenem, antibiotic levels will be measured from the infusion bag at the beginning and end of the infusion to determine the amount of degradation of these antibiotics.
The temperature of the infusion bags will be monitored continuously during this time.
Pseudomonas aeruginosa virulence gene determinants
A panel of different previously identified virulence gene determinants for Pseudomonas aeruginosa will be measured by RNA analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01667094
Brief Title
A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
Acronym
CISTIC
Official Title
Continuous-infusion Anti-pseudomonal β-lactams for the Treatment of Acute, Infective Pulmonary Exacerbations in Cystic Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Unknown status
Study Start Date
September 2012 (undefined)
Primary Completion Date
July 2017 (Anticipated)
Study Completion Date
July 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Alfred
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Pulmonary exacerbation, Continuous infusion, Antipseudomonal beta-lactams
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intermittent, short infusion
Arm Type
Active Comparator
Arm Description
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
Arm Title
Continuous infusion
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Intermittent, short infusion Ceftazidime
Intervention Description
Ceftazidime 1g q8/24
Intervention Type
Drug
Intervention Name(s)
Continuous infusion Ceftazidime
Intervention Description
Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24
Intervention Type
Drug
Intervention Name(s)
Intermittent, short infusion Meropenem
Intervention Description
Meropenem 1g q8/24, infusion over 30 minutes
Intervention Type
Drug
Intervention Name(s)
Continuous infusion Meropenem
Intervention Description
Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24
Intervention Type
Drug
Intervention Name(s)
Intermittent, short infusion Ticarcillin-clavulanate
Intervention Description
Ticarcillin/clavulanate 3.1g q6/24
Intervention Type
Drug
Intervention Name(s)
Continuous infusion Ticarcillin-clavulanate
Intervention Description
Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24
Intervention Type
Drug
Intervention Name(s)
Intermittent, short infusion Cefepime
Intervention Description
Cefepime 1g q8/24
Intervention Type
Drug
Intervention Name(s)
Continuous infusion Cefepime
Intervention Description
Cefepime loading dose 500mg followed by 1.5g infused over 12/24, q12/24
Intervention Type
Drug
Intervention Name(s)
Continuous infusion Piperacillin tazobactam
Intervention Description
Piperacillin tazobactam loading dose of 4.5g infused over 30 minutes followed by 18g infused over 24/24, q24/24
Intervention Type
Drug
Intervention Name(s)
Intermittent, short infusion Piperacillin tazobactam
Intervention Description
Piperacillin tazobactam 4.5g q6/24
Primary Outcome Measure Information:
Title
Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score
Time Frame
Day 0 to Day 14
Secondary Outcome Measure Information:
Title
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score
Time Frame
Day 0 to Day 7, Day 0 to Day 28
Title
Lung function testing; Forced volume expired in one second (FEV1)
Time Frame
Day 0 to Day 7, Day 0 to Day 28
Title
C-reactive peptide (CRP)
Time Frame
Day 0 to Day 3
Title
Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)
Description
Measured by PCR.
Time Frame
Day 0 to Day 3, Day 0 to Day 7
Title
Time above minimum inhibitory concentration (MIC)
Time Frame
Day 3
Title
Antibiotic stability
Description
For ceftazidime and meropenem, antibiotic levels will be measured from the infusion bag at the beginning and end of the infusion to determine the amount of degradation of these antibiotics.
The temperature of the infusion bags will be monitored continuously during this time.
Time Frame
Day 3
Title
Pseudomonas aeruginosa virulence gene determinants
Description
A panel of different previously identified virulence gene determinants for Pseudomonas aeruginosa will be measured by RNA analysis.
Time Frame
Day 0 to Day 3 and Day 0 to Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients >= 18 years of age,
Pseudomonas aeruginosa isolated in sputum within the last 12 months,
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
Exclusion Criteria:
patients < 18 yrs of age,
patients that do not meet the criteria for an acute infective exacerbation,
concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory failure,
impaired renal function with an estimated creatinine clearance < 60 mls/min,
patients allergic to ß-lactam antibiotics,
aminoglycoside contra-indicated,
intravenous antibiotics in the last 2 weeks, prior to this admission,
received more than 24 hours of intravenous antibiotics in this admission,
previous lung transplantation,
pregnancy or lactation, or
inability to consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anton Peleg, MBBS, FRACP.
Organizational Affiliation
The Alfred
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
12. IPD Sharing Statement
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A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis
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