A Study Comparing Continuous Infusion Antibiotics to Standard Treatment for Lung Infections in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— CISTIC  

Official title:

Continuous-infusion Anti-pseudomonal β-lactams for the Treatment of Acute, Infective Pulmonary Exacerbations in Cystic Fibrosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01667094
• Other study ID #: 249/12
• Secondary ID: U1111-1132-8291
• Status: Active, not recruiting
• Phase: Phase 4
• First received: August 13, 2012
• Last updated: April 18, 2017
• Start date: September 2012
• Est. completion date: July 2017

Study information

• Verified date: April 2017
• Source: The Alfred
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Intermittent, short infusion Ceftazidime
Ceftazidime 1g q8/24
• Continuous infusion Ceftazidime
Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24
• Intermittent, short infusion Meropenem
Meropenem 1g q8/24, infusion over 30 minutes
• Continuous infusion Meropenem
Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24
• Intermittent, short infusion Ticarcillin-clavulanate
Ticarcillin/clavulanate 3.1g q6/24
• Continuous infusion Ticarcillin-clavulanate
Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24
• Intermittent, short infusion Cefepime
Cefepime 1g q8/24
• 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
• Intermittent, short infusion Piperacillin tazobactam
Piperacillin tazobactam 4.5g q6/24

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
The Alfred

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score		Day 0 to Day 14
Secondary	Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score		Day 0 to Day 7, Day 0 to Day 28
Secondary	Lung function testing; Forced volume expired in one second (FEV1)		Day 0 to Day 7, Day 0 to Day 28
Secondary	C-reactive peptide (CRP)		Day 0 to Day 3
Secondary	Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)	Measured by PCR.	Day 0 to Day 3, Day 0 to Day 7
Secondary	Time above minimum inhibitory concentration (MIC)		Day 3
Secondary	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.	Day 3
Secondary	Pseudomonas aeruginosa virulence gene determinants	A panel of different previously identified virulence gene determinants for Pseudomonas aeruginosa will be measured by RNA analysis.	Day 0 to Day 3 and Day 0 to Day 7