Overview

This trial is active, not recruiting.

Condition cystic fibrosis
Treatments 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
Phase phase 4
Sponsor The Alfred
Start date September 2012
End date September 2016
Trial size 50 participants
Trial identifier NCT01667094, 249/12, U1111-1132-8291

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
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
intermittent, short infusion ceftazidime
Ceftazidime 1g q8/24
intermittent, short infusion meropenem
Meropenem 1g q8/24, infusion over 30 minutes
intermittent, short infusion ticarcillin-clavulanate
Ticarcillin/clavulanate 3.1g q6/24
intermittent, short infusion cefepime
Cefepime 1g q8/24
intermittent, short infusion piperacillin tazobactam
Piperacillin tazobactam 4.5g q6/24
(Experimental)
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
continuous infusion ceftazidime
Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24
continuous infusion meropenem
Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24
continuous infusion ticarcillin-clavulanate
Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24
continuous infusion cefepime
Cefepime loading dose 500mg followed by 1.5g infused over 12/24, q12/24
continuous infusion piperacillin tazobactam
Piperacillin tazobactam loading dose of 4.5g infused over 30 minutes followed by 18g infused over 24/24, q24/24

Primary Outcomes

Measure
Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score
time frame: Day 0 to Day 14

Secondary Outcomes

Measure
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score
time frame: Day 0 to Day 7, Day 0 to Day 28
Lung function testing; Forced volume expired in one second (FEV1)
time frame: Day 0 to Day 7, Day 0 to Day 28
C-reactive peptide (CRP)
time frame: Day 0 to Day 3
Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)
time frame: Day 0 to Day 3, Day 0 to Day 7
Time above minimum inhibitory concentration (MIC)
time frame: Day 3
Antibiotic stability
time frame: Day 3
Pseudomonas aeruginosa virulence gene determinants
time frame: Day 0 to Day 3 and Day 0 to Day 7

Eligibility Criteria

Male or female participants at least 18 years old.

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 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.

Additional Information

Official title Continuous-infusion Anti-pseudomonal β-lactams for the Treatment of Acute, Infective Pulmonary Exacerbations in Cystic Fibrosis
Principal investigator Anton Peleg, MBBS, FRACP.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by The Alfred.