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

This study is not yet open for participant recruitment.
Verified August 2012 by The Alfred
Sponsor:
Information provided by (Responsible Party):
Katherine Langan, The Alfred
ClinicalTrials.gov Identifier:
NCT01667094
First received: August 13, 2012
Last updated: August 15, 2012
Last verified: August 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
 Drug: Intermittent, short infusion Ceftazidime
Drug: Continuous infusion Ceftazidime
Drug: Intermittent, short infusion Meropenem
Drug: Continuous infusion Meropenem
Drug: Intermittent, short infusion Ticarcillin-clavulanate
Drug: Continuous infusion Ticarcillin-clavulanate
Drug: Intermittent, short infusion Cefepime
Drug: Continuous infusion Cefepime
Drug: Continuous infusion Piperacillin tazobactam
Drug: Intermittent, short infusion Piperacillin tazobactam
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Continuous-infusion Anti-pseudomonal β-lactams for the Treatment of Acute, Infective Pulmonary Exacerbations in Cystic Fibrosis: a Prospective Randomised Controlled Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The Alfred:

Primary Outcome Measures:
  • Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score [ Time Frame: Day 0 to Day 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory symptom score [ Time Frame: Day 0 to Day 7, Day 0 to Day 28 ] [ Designated as safety issue: No ]
  • Lung function testing; Forced volume expired in one second (FEV1) [ Time Frame: Day 0 to Day 7, Day 0 to Day 28 ] [ Designated as safety issue: No ]
  • C-reactive peptide (CRP) [ Time Frame: Day 0 to Day 3 ] [ Designated as safety issue: No ]
  • Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa) [ Time Frame: Day 0 to Day 3, Day 0 to Day 7 ] [ Designated as safety issue: No ]
    Measured by PCR.

  • Time above minimum inhibitory concentration (MIC) [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
  • Antibiotic stability [ Time Frame: Day 3 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Day 0 to Day 3 and Day 0 to Day 7 ] [ Designated as safety issue: No ]
    A panel of different previously identified virulence gene determinants for Pseudomonas aeruginosa will be measured by RNA analysis.


Estimated Enrollment: 120
Study Start Date: September 2012
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

 Drug: Intermittent, short infusion Ceftazidime
Ceftazidime 1g q8/24
Drug: Intermittent, short infusion Meropenem
Meropenem 1g q8/24, infusion over 30 minutes
Drug: Intermittent, short infusion Ticarcillin-clavulanate
Ticarcillin/clavulanate 3.1g q6/24
Drug: Intermittent, short infusion Cefepime
Cefepime 1g q8/24
Drug: Intermittent, short infusion Piperacillin tazobactam
Piperacillin tazobactam 4.5g q8/24
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

 Drug: Continuous infusion Ceftazidime
Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24
Drug: Continuous infusion Meropenem
Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24
Drug: Continuous infusion Ticarcillin-clavulanate
Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24
Drug: Continuous infusion Cefepime
Cefepime loading dose 500mg followed by 1.5g infused over 12/24, q12/24
Drug: Continuous infusion Piperacillin tazobactam
Piperacillin tazobactam loading dose of 2.25g infused over 30 minutes followed by 12.4g infused over 24/24, q24/24

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. previous enrolment in the study,
  4. concurrent pulmonary embolism, significant haemoptysis, pneumothorax, or respiratory failure,
  5. impaired renal function with an estimated creatinine clearance < 60 mls/min,
  6. patients allergic to ß-lactam antibiotics,
  7. aminoglycoside contra-indicated,
  8. intravenous antibiotics in the last 2 weeks, prior to this admission,
  9. received more than 24 hours of intravenous antibiotics in this admission,
  10. previous lung transplantation,
  11. pregnancy or lactation, or
  12. inability to consent.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01667094

Contacts
Contact: Katherine LANGAN, BMBS 613 9076 2000 Katherine.Langan@monash.edu.au

Locations
Australia, Victoria
The Alfred Hospital Not yet recruiting
Melbourne, Victoria, Australia, 3181
Sponsors and Collaborators
The Alfred
Investigators
Principal Investigator: Anton Peleg, MBBS, FRACP. The Alfred Hospital
  More Information

No publications provided

Responsible Party: Katherine Langan, PhD, The Alfred
ClinicalTrials.gov Identifier: NCT01667094     History of Changes
Other Study ID Numbers: 249/12, U1111-1132-8291
Study First Received: August 13, 2012
Last Updated: August 15, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by The Alfred:
Pulmonary exacerbation
Continuous infusion
Antipseudomonal beta-lactams

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Anti-Bacterial Agents
Ticarcillin
Ceftazidime
Piperacillin
 Cefepime
Clavulanic Acids
Clavulanic Acid
Meropenem
Penicillanic Acid
Ticarcillin-clavulanic acid
Piperacillin-tazobactam combination product
Tazobactam
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013