Continuous-infusion Anti-pseudomonal β-lactams for the Treatment of Acute, Infective Pulmonary Exacerbations in Cystic Fibrosis
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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
Intervention: Intermittent, short infusion Ceftazidime (Drug)
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
Intervention: Intermittent, short infusion Meropenem (Drug)
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
Intervention: Intermittent, short infusion Ticarcillin-clavulanate (Drug)
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
Intervention: Intermittent, short infusion Cefepime (Drug)
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
Intervention: Intermittent, short infusion Piperacillin tazobactam (Drug)
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
Intervention: Continuous infusion Ceftazidime (Drug)
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
Intervention: Continuous infusion Meropenem (Drug)
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
Intervention: Continuous infusion Ticarcillin-clavulanate (Drug)
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
Intervention: Continuous infusion Cefepime (Drug)
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
Intervention: Continuous infusion Piperacillin tazobactam (Drug)
Outcomes
Primary Outcomes
Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score
Time Frame: Day 0 to Day 14
Secondary Outcomes
- Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)(Day 0 to Day 3, Day 0 to Day 7)
- Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score(Day 0 to Day 7, Day 0 to Day 28)
- Lung function testing; Forced volume expired in one second (FEV1)(Day 0 to Day 7, Day 0 to Day 28)
- C-reactive peptide (CRP)(Day 0 to Day 3)
- Time above minimum inhibitory concentration (MIC)(Day 3)
- Antibiotic stability(Day 3)
- Pseudomonas aeruginosa virulence gene determinants(Day 0 to Day 3 and Day 0 to Day 7)
Investigators
Katherine Langan
PhD
The Alfred