NCT01667094

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Sep 2012

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 13, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 17, 2012

Completed
15 days until next milestone

Study Start

First participant enrolled

September 1, 2012

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2017

Completed
Last Updated

April 20, 2017

Status Verified

April 1, 2017

Enrollment Period

4.8 years

First QC Date

August 13, 2012

Last Update Submit

April 18, 2017

Conditions

Keywords

Pulmonary exacerbationContinuous infusionAntipseudomonal beta-lactams

Outcome Measures

Primary Outcomes (1)

  • Cystic Fibrosis Questionnaire-Revised respiratory component (CFQ-R) respiratory symptom score

    Day 0 to Day 14

Secondary Outcomes (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

  • Quantitative bacterial load in sputum (total + Pseudomonas aeruginosa)

    Day 0 to Day 3, Day 0 to Day 7

  • Time above minimum inhibitory concentration (MIC)

    Day 3

  • +2 more secondary outcomes

Study Arms (2)

Intermittent, short infusion

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

Drug: Intermittent, short infusion CeftazidimeDrug: Intermittent, short infusion MeropenemDrug: Intermittent, short infusion Ticarcillin-clavulanateDrug: Intermittent, short infusion CefepimeDrug: Intermittent, short infusion Piperacillin tazobactam

Continuous infusion

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

Drug: Continuous infusion CeftazidimeDrug: Continuous infusion MeropenemDrug: Continuous infusion Ticarcillin-clavulanateDrug: Continuous infusion CefepimeDrug: Continuous infusion Piperacillin tazobactam

Interventions

Ceftazidime 1g q8/24

Intermittent, short infusion

Ceftazidime loading dose 1g infused over 30mins then 3g infused over 12h q12/24

Continuous infusion

Meropenem 1g q8/24, infusion over 30 minutes

Intermittent, short infusion

Meropenem initial loading dose of 500mg infused over 30 minutes followed by 1.5g infused over 12/24, q12/24

Continuous infusion

Ticarcillin/clavulanate 3.1g q6/24

Intermittent, short infusion

Ticarcillin-clavulanate loading dose 1.55g followed by 12.4g infused over 24/24 q24/24

Continuous infusion

Cefepime 1g q8/24

Intermittent, short infusion

Cefepime loading dose 500mg followed by 1.5g infused over 12/24, q12/24

Continuous infusion

Piperacillin tazobactam loading dose of 4.5g infused over 30 minutes followed by 18g infused over 24/24, q24/24

Continuous infusion

Piperacillin tazobactam 4.5g q6/24

Intermittent, short infusion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant, Newborn, Diseases

Study Officials

  • Anton Peleg, MBBS, FRACP.

    The Alfred

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
PhD

Study Record Dates

First Submitted

August 13, 2012

First Posted

August 17, 2012

Study Start

September 1, 2012

Primary Completion

July 1, 2017

Study Completion

July 1, 2017

Last Updated

April 20, 2017

Record last verified: 2017-04

Locations