Cystic FibrosisPhase 2NCT00786513
Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy
A Phase 2 study testing Conventional antimicrobial susceptibility testing and Biofilm antimicrobial susceptibility testing in people with Cystic Fibrosis, run by The Hospital for Sick Children at 5 sites in Canada.
Trial summary
The purpose of this study is to determine whether choosing antibiotics based on a biofilm antimicrobial susceptibility assay rather than a conventional planktonic antimicrobial susceptibility assay to treat CF patients with chronic P. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Conventional antimicrobial susceptibility testing and Biofilm antimicrobial susceptibility testing
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 5 sitesCanada
- Study dates
- Nov 2008to Mar 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of CF based on the following: sweat chloride > 60 mEq/L or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF
- Chronically infected with P. aeruginosa (>50% of respiratory specimens positive for P. aeruginosa in the 24 months prior to screening)
- Able to produce sputum (expectorated or induced)
- Able to reproducibility perform pulmonary function testing
- Written informed consent provided
Who cannot join
- Sputum culture negative for P. aeruginosa or with a density of less that 10^5 CFU/g at screening
- Sputum culture positive for Burkholderia cepacia at screening
- History of B. cepacia positive respiratory culture within 24 months prior to screening
- Use of antibiotics other than those prescribed by the principal investigator
- History of allergy (urticarial rash, diffuse erythroderma, serum sickness) to more than two groups of antibiotics (aminoglycosides, penicillins, cephalosporins, monobactams, macrolides, or quinolones) that are a therapeutic option
- History of anaphylaxis or other life threatening complication to any antibiotic in the six groups that are a therapeutic option
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- Post lung transplantation or listed for lung transplantation
- Pregnancy
- A septic or clinically unstable patient
- Presence of a condition or abnormality that in the opinion of an investigator would compromise the safety of the patient or the quality of the data
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
Hamilton Health Sciences
Hamilton, Ontario
St. Michael's Hospital
Toronto, Ontario
The Hospital for Sick Children
Toronto, Ontario
BC Children's Hospital
Vancouver, British Columbia
St. Paul's Hospital
Vancouver, British Columbia
About this study
Official title: Randomized Double Blind Controlled Trial of the Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy in Chronic Pseudomonas Aeruginosa Infected Cystic Fibrosis Patients
The purpose of this study is to determine whether choosing antibiotics based on a biofilm antimicrobial susceptibility assay rather than a conventional planktonic antimicrobial susceptibility assay to treat CF patients with chronic P. aeruginosa infection with an acute pulmonary exacerbation is a safe intervention that will result in improved microbiological and clinical outcomes and decrease markers of pulmonary inflammation.
Read the detailed description
Cystic fibrosis (CF) is the most common fatal genetic condition in the Caucasian population and affects over 3,000 Canadians. Respiratory failure caused by chronic pulmonary infection is the primary cause of death in CF patients. The improved life expectancy of CF patients in the past several decades is due in part to the more aggressive use of antibiotics in the treatment of respiratory infections. However, there is currently no antimicrobial susceptibility assay that can predict which antibiotics will result in improved patient outcomes. Since Pseudomonas aeruginosa is known to grow as a resistant biofilm in the CF lung, antimicrobial susceptibility testing based on biofilm growth of P. aeruginosa may lead to different antibiotic choices that significantly decrease the pulmonary bacterial density of P. aeruginosa. A biofilm antimicrobial susceptibility assay thus has the ability to change the way antibiotics are chosen to treat CF patients and result in improved lung function and longer lives for all CF patients.
- Conditions
- Cystic Fibrosis
- Being tested
- Conventional antimicrobial susceptibility testing, Biofilm antimicrobial susceptibility testing
- Keywords
- Cystic fibrosis, Pseudomonas aeruginosa, biofilm, antibiotic susceptibility testing, pediatrics
- Medical subject headings
- Cystic Fibrosis, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional antimicrobial susceptibility testingOther
Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on conventional planktonic antimicrobial susceptibility testing results.
Biofilm antimicrobial susceptibility testingOther
Subjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on biofilm antimicrobial susceptibility testing results.
| Study group | Role | What they receive |
|---|---|---|
| Control Arm | Active comparator | Not described Receives: Other: Conventional antimicrobial susceptibility testing |
| Intervention Arm | Experimental | Not described Receives: Other: Biofilm antimicrobial susceptibility testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients in the intervention arm versus the control arm who have ≥ 3 log drop in colony forming units (CFUs) of P. aeruginosa in sputum.
Measured: Measured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit
Secondary outcomes (4)
The change in pulmonary function tests, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal midexpiratory flow rate (FEF25-75) in the intervention arm versus the control arm
Measured: Measured at day 0, day 7, and day 14 of antibiotic treatment and at the 1 month follow-up visit
The time to subsequent acute pulmonary exacerbation in the intervention arm versus the control arm
Measured: 1 year following the completion of antibiotic therapy
The change in the cumulative score on a quality of life questionnaire in the intervention arm versus the control arm
Measured: Measued at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit
The change in the measurement of markers of pulmonary inflammation (neutrophil counts, neutrophil elastase and IL-8 levels in sputum) in the intervention arm versus the control arm.
Measured: Meaured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Valerie Waters, The Hospital for Sick Children
- Investigators
- Valerie Waters, MD, Principal investigator, The Hospital for Sick ChildrenYvonne Yau, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00786513
- Sponsor's protocol ID
- 1000011132
- Status last verified
- Apr 2014
- First submitted
- 5 Nov 2008
- Last updated
- 4 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Yau YC, Ratjen F, Tullis E, Wilcox P, Freitag A, Chilvers M, Grasemann H, Zlosnik J, Speert D, Corey M, Stanojevic S, Matukas L, Leahy TR, Shih S, Waters V. Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients. J Cyst Fibros. 2015 Mar;14(2):262-6. doi: 10.1016/j.jcf.2014.09.013. Epub 2014 Oct 30.
PubMed 25453872
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Double Blind Controlled Trial of the Use of a Biofilm Antimicrobial Susceptibility Assay to Guide Antibiotic Therapy in Chronic Pseudomonas Aeruginosa Infected Cystic Fibrosis Patients
- ClinicalTrials.gov ID
- NCT00786513
- Acronym / sponsor ID
- 1000011132
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic fibrosis, Pseudomonas aeruginosa, biofilm, antibiotic susceptibility testing, pediatrics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 6 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether choosing antibiotics based on a biofilm antimicrobial susceptibility assay rather than a conventional planktonic antimicrobial susceptibility assay to treat CF patients with chronic P. aeruginosa infection with an acute pulmonary exacerbation is a safe intervention that will result in improved microbiological and clinical outcomes and decrease markers of pulmonary inflammation.
Detailed description
Cystic fibrosis (CF) is the most common fatal genetic condition in the Caucasian population and affects over 3,000 Canadians. Respiratory failure caused by chronic pulmonary infection is the primary cause of death in CF patients. The improved life expectancy of CF patients in the past several decades is due in part to the more aggressive use of antibiotics in the treatment of respiratory infections. However, there is currently no antimicrobial susceptibility assay that can predict which antibiotics will result in improved patient outcomes. Since Pseudomonas aeruginosa is known to grow as a resistant biofilm in the CF lung, antimicrobial susceptibility testing based on biofilm growth of P. aeruginosa may lead to different antibiotic choices that significantly decrease the pulmonary bacterial density of P. aeruginosa. A biofilm antimicrobial susceptibility assay thus has the ability to change the way antibiotics are chosen to treat CF patients and result in improved lung function and longer lives for all CF patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Arm | Active comparator | Other: Conventional antimicrobial susceptibility testing |
| Intervention Arm | Experimental | Other: Biofilm antimicrobial susceptibility testing |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of CF based on the following: sweat chloride > 60 mEq/L or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF
- Chronically infected with P. aeruginosa (>50% of respiratory specimens positive for P. aeruginosa in the 24 months prior to screening)
- Able to produce sputum (expectorated or induced)
- Able to reproducibility perform pulmonary function testing
- Written informed consent provided
Key exclusion criteria (10 listed)
- Sputum culture negative for P. aeruginosa or with a density of less that 10^5 CFU/g at screening
- Sputum culture positive for Burkholderia cepacia at screening
- History of B. cepacia positive respiratory culture within 24 months prior to screening
- Use of antibiotics other than those prescribed by the principal investigator
- History of allergy (urticarial rash, diffuse erythroderma, serum sickness) to more than two groups of antibiotics (aminoglycosides, penicillins, cephalosporins, monobactams, macrolides, or quinolones) that are a therapeutic option
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conventional antimicrobial susceptibility testingSubjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on conventional planktonic antimicrobial susceptibility testing results. | Other | Control Arm |
| Biofilm antimicrobial susceptibility testingSubjects in this arm will be prescribed 14 days of an intravenous 2 drug antibiotic combination based on biofilm antimicrobial susceptibility testing results. | Other | Intervention Arm |
Primary outcome
The proportion of patients in the intervention arm versus the control arm who have ≥ 3 log drop in colony forming units (CFUs) of P. aeruginosa in sputum.
Time frame: Measured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit
4 secondary outcomes
The change in pulmonary function tests, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and maximal midexpiratory flow rate (FEF25-75) in the intervention arm versus the control arm
Time frame: Measured at day 0, day 7, and day 14 of antibiotic treatment and at the 1 month follow-up visit
The time to subsequent acute pulmonary exacerbation in the intervention arm versus the control arm
Time frame: 1 year following the completion of antibiotic therapy
The change in the cumulative score on a quality of life questionnaire in the intervention arm versus the control arm
Time frame: Measued at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit
The change in the measurement of markers of pulmonary inflammation (neutrophil counts, neutrophil elastase and IL-8 levels in sputum) in the intervention arm versus the control arm.
Time frame: Meaured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2014.
- Derived from this study: PubMed 25453872Yau YC, Ratjen F, Tullis E, Wilcox P, Freitag A, Chilvers M, Grasemann H, Zlosnik J, Speert D, Corey M, Stanojevic S, Matukas L, Leahy TR, Shih S, Waters V. Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients. J Cyst Fibros. 2015 Mar;14(2):262-6. doi: 10.1016/j.jcf.2014.09.013. Epub 2014 Oct 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Valerie Waters, MD principal investigator
The Hospital for Sick Children
Yvonne Yau, MD principal investigator
The Hospital for Sick Children
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Conventional antimicrobial susceptibility testing and Biofilm antimicrobial susceptibility testing in people with Cystic Fibrosis, run by The Hospital for Sick Children at 5 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of patients in the intervention arm versus the control arm who have ≥ 3 log drop in colony forming units (CFUs) of P. aeruginosa in sputum. (time frame: Measured at day 0 and day 14 of antibiotic treatment and at the 1 month follow-up visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00786513, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2014.