Cystic FibrosisPhase 2NCT00298922
Azithromycin in Patients With CF, Infected With Burkholderia Cepacia Complex
A Phase 2 study testing Azithromycin in people with Cystic Fibrosis, run by Unity Health Toronto at 1 site in Canada.
Trial summary
Pulmonary infection with Burkholderia cepacia complex (BCC) in patients with CF is often associated with a more rapid decline in lung function. Because of the resistance of BCC to many antibiotics, treatment options are often limited. New therapies to improve outcomes for patients infected with BCC are needed. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2006to Oct 2009
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent and verbal assent as appropriate has been provided by the subject
- Ability to comply with medication use, study visits and study procedures as judged by the site Investigator
- Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
- > 18 years of age
- Body weight > 40 kg
- BCC present in a sputum/throat culture > 1 year prior to screening and at screening
Show all 10Show fewer
- FEV1 % predicted > 30% as calculated by the Knudsen reference equations
- Room air oximetry > 88% at rest
- Post-menarche females must be surgically sterile or using an effective form of contraception
- Predicted to live > 1 year and clinically stable at that time of enrollment as judged by the investigator.
Who cannot join
- History of chronic macrolide use, defined as regular macrolide antibiotic use within a three month period prior to enrollment in the study.
- AST or ALT > 2.5 times the upper limit of normal performed at the local laboratories on two occasions prior to randomization.
- Investigational drug use within 30 days of screening
- History of alcohol, illicit drug or medication abuse within 1 year of screening
- Use of intravenous antibiotics or oral antibiotics within 14 days of screening.
- Use of low dose oral antibiotics (e.g. macrolides, tetracycline, sulfa) for acne or other conditions within 30 days of screening
Show all 16Show fewer
- Use of systemic corticosteroids (> 20 mg of prednisone per day) within 30 days of screening
- Initiation of TOBI®, high dose ibuprofen, or rhDNase within 60 days of screening
- History of lung transplantation or currently on lung transplant list
- History of allergy to a macrolide antibiotic
- AFB smear positive at screening suggesting current NTM infection.
- Positive serum pregnancy test at screening (to be performed on all post-menarche females)
- Absolute neutrophil count < 1000 performed at the local laboratories on two occasions prior to randomization
- Creatinine > 1.5 times normal performed at the local laboratories on two occasions prior to randomization.
- Chest x-ray changes or physical findings at screening that would compromise the safety of the patient or the quality of the study data
- Other major organ dysfunction
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II, Randomized, Double Blind, Placebo-Controlled Trial of Azithromycin in Patients With CF, Chronically Infected With Burkholderia Cepacia Complex
Pulmonary infection with Burkholderia cepacia complex (BCC) in patients with CF is often associated with a more rapid decline in lung function. Because of the resistance of BCC to many antibiotics, treatment options are often limited. New therapies to improve outcomes for patients infected with BCC are needed.
However, because of the unpredictable nature of this pulmonary infection in CF, patients with BCC infection have been excluded from many CF therapeutic trials.
Read more
Recent published trials in the United States, Australia, and the United Kingdom have all demonstrated clinical benefits from prolonged administration of azithromycin in CF. In these trials, the vast majority of patients were chronically infected with Pseudomonas aeruginosa.
Patients with BCC were excluded from the US and UK trials, and only four patients with BCC infection were enrolled in the Australian trial. Thus, the effectiveness of azithromycin in CF patients infected with BCC is largely unknown and deserves further study.
The two main ways by which azithromycin is thought to help with the chronic lung infections seen in CF are by [a] reducing inflammation and [b] direct effects on the bacteria, in particular P. aeruginosa. BCC pulmonary infection in CF is often associated with a large inflammatory response similar to or more severe than P. aeruginosa infection. If azithromycin works mainly by an anti-inflammatory mechanism, it should also be helpful in CF patients infected with BCC.
Alternatively, azithromycin could have a direct effect on BCC as seen with P. aeruginosa as the two bacteria have many similarities.
Read the detailed description
STUDY DESIGN
- Overview
- This is a single center, randomized, double-blinded, placebo-controlled 24 week trial of azithromycin in adults with CF chronically infected with BCC. The investigational therapy will be added to usual therapy in patients who are clinically stable at the time of enrollment. After 168 days, the study drug will be discontinued and participants will be evaluated at 196 days off of study drug for 28 days. At that visit, participants will be invited to continue in an open label observational study of azithromycin for 168 additional days. Thus, the duration of the study will be 52 weeks (364 days).
- Day 0- Day 168 on Study Drug (24 weeks)
- Day 169- Day 196 off Study Drug (4 weeks)
- Day 197 - Day 364 on OPEN label Azithromycin (24 weeks)
- Measuring primary and secondary endpoints
- Primary efficacy endpoint
- Primary efficacy endpoint will be the quantitative changes in lung function as measured by FEV1 in % predicted from baseline to completion of the 24 week treatment period. (refer to Appendix C for ATS guidelines).
- Primary safety endpoints
- Primary safety endpoints collected over the 24 week treatment period will be:
- Adverse events such as gastrointestinal complaints, ototoxicity, tinnitus, hepatitis or leukopenia as determined by: (i) open ended questioning of study subjects at study visits (ii) laboratory tests for elevated liver function tests or hematologic abnormalities,
- Changes in lung microbiology as determined by:[86] (i) Emergent B. cenocepacia (genomovar III) (ii) Emergent non-B. cenocepacia genomovars (iii) Emergent NTM[87] (iv) Emergent azithromycin resistant NTM (v) Emergent Aspergillus species (vi) Emergent MDRO - (S. maltophilia, A. xylosoxidans, or methicillin-resistant S. aureus) (vii) Emergent P. aeruginosa (viii) Emergent azithromycin resistant S. aureus
- Secondary efficacy endpoints
- Secondary efficacy endpoints will be:
- Quantitative changes in lung function as measured by change in relative percent change in FEV1 and FVC from baseline to completion of the 24 week treatment period.
- Quantitative change in FEV1 and FVC in liters in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo. FEV1 and FVC in liters will be measured according to ATS criteria
- The number of days until first administration of intravenous antibiotics and/or the use of oral tetracycline derivatives minocycline / doxycycline for seven or more days during the 24 week period.
- The number of pulmonary exacerbations as defined by need for treatment with intravenous or oral tetracycline derivative antibiotics for an increase in pulmonary symptoms during the 24 week period.
- The proportion of patients requiring intravenous antibiotics during the 24 week period.
- The number of days of treatment with intravenous antibiotics given during the 24 week period.
- The proportion of patients hospitalized.
- The number of hospital days as calculated by calendar days during the 24 week period.
- The proportion of patients requiring oral antibiotics during the 24 week period.
- The number of days of treatment with oral non-tetracycline derivative antibiotics given during the 24 week period.
- Changes in body weight from baseline to completion of the 24 week treatment period.
- Change in level of inflammation as measured by the change in serum CRP and ESR from baseline to the end of the 24 week treatment period.
- Conditions
- Cystic Fibrosis
- Being tested
- Azithromycin, Placebo
- Keywords
- Cystic Fibrosis, Burkholderia cepacia complex
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
500 mg tablets orally thrice weekly for 24 weeks
PlaceboDrug
tablet orally thrice weekly for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin | Active comparator | participants taking 500 mg tablets orally thrice weekly for 24 weeks Receives: Drug: Azithromycin |
| Placebo | Placebo comparator | Participants taking 500 mg tablets orally thrice weekly for 24 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in FEV1 in % predicted in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2006 (estimated)
- Study startFeb 2006
- Primary completionFeb 2009 (estimated)
- Study completionOct 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Foundation, Pfizer
- Investigators
- Elizabeth Tullis, MD, Principal investigator, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00298922
- Sponsor's protocol ID
- AZ 0003
- Other IDs
- TULLIS04A0
- Status last verified
- Jul 2009
- First submitted
- 2 Mar 2006
- Last updated
- 31 Jul 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Randomized, Double Blind, Placebo-Controlled Trial of Azithromycin in Patients With CF, Chronically Infected With Burkholderia Cepacia Complex
- ClinicalTrials.gov ID
- NCT00298922
- Acronym / sponsor ID
- AZ 0003
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Burkholderia cepacia complex
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Foundation, Pfizer
- Study start
- Feb 2006
- Primary completion
- Feb 2009 (estimated)
- Study completion
- Oct 2009 (estimated)
- First posted
- 3 Mar 2006 (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.
Pulmonary infection with Burkholderia cepacia complex (BCC) in patients with CF is often associated with a more rapid decline in lung function. Because of the resistance of BCC to many antibiotics, treatment options are often limited. New therapies to improve outcomes for patients infected with BCC are needed.
However, because of the unpredictable nature of this pulmonary infection in CF, patients with BCC infection have been excluded from many CF therapeutic trials.
Recent published trials in the United States, Australia, and the United Kingdom have all demonstrated clinical benefits from prolonged administration of azithromycin in CF. In these trials, the vast majority of patients were chronically infected with Pseudomonas aeruginosa.
Patients with BCC were excluded from the US and UK trials, and only four patients with BCC infection were enrolled in the Australian trial. Thus, the effectiveness of azithromycin in CF patients infected with BCC is largely unknown and deserves further study.
The two main ways by which azithromycin is thought to help with the chronic lung infections seen in CF are by [a] reducing inflammation and [b] direct effects on the bacteria, in particular P. aeruginosa. BCC pulmonary infection in CF is often associated with a large inflammatory response similar to or more severe than P. aeruginosa infection. If azithromycin works mainly by an anti-inflammatory mechanism, it should also be helpful in CF patients infected with BCC.
Alternatively, azithromycin could have a direct effect on BCC as seen with P. aeruginosa as the two bacteria have many similarities.
Detailed description
STUDY DESIGN
- Overview
- This is a single center, randomized, double-blinded, placebo-controlled 24 week trial of azithromycin in adults with CF chronically infected with BCC. The investigational therapy will be added to usual therapy in patients who are clinically stable at the time of enrollment. After 168 days, the study drug will be discontinued and participants will be evaluated at 196 days off of study drug for 28 days. At that visit, participants will be invited to continue in an open label observational study of azithromycin for 168 additional days. Thus, the duration of the study will be 52 weeks (364 days).
- Day 0- Day 168 on Study Drug (24 weeks)
- Day 169- Day 196 off Study Drug (4 weeks)
- Day 197 - Day 364 on OPEN label Azithromycin (24 weeks)
- Measuring primary and secondary endpoints
- Primary efficacy endpoint
- Primary efficacy endpoint will be the quantitative changes in lung function as measured by FEV1 in % predicted from baseline to completion of the 24 week treatment period. (refer to Appendix C for ATS guidelines).
- Primary safety endpoints
- Primary safety endpoints collected over the 24 week treatment period will be:
- Adverse events such as gastrointestinal complaints, ototoxicity, tinnitus, hepatitis or leukopenia as determined by: (i) open ended questioning of study subjects at study visits (ii) laboratory tests for elevated liver function tests or hematologic abnormalities,
- Changes in lung microbiology as determined by:[86] (i) Emergent B. cenocepacia (genomovar III) (ii) Emergent non-B. cenocepacia genomovars (iii) Emergent NTM[87] (iv) Emergent azithromycin resistant NTM (v) Emergent Aspergillus species (vi) Emergent MDRO - (S. maltophilia, A. xylosoxidans, or methicillin-resistant S. aureus) (vii) Emergent P. aeruginosa (viii) Emergent azithromycin resistant S. aureus
- Secondary efficacy endpoints
- Secondary efficacy endpoints will be:
- Quantitative changes in lung function as measured by change in relative percent change in FEV1 and FVC from baseline to completion of the 24 week treatment period.
- Quantitative change in FEV1 and FVC in liters in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo. FEV1 and FVC in liters will be measured according to ATS criteria
- The number of days until first administration of intravenous antibiotics and/or the use of oral tetracycline derivatives minocycline / doxycycline for seven or more days during the 24 week period.
- The number of pulmonary exacerbations as defined by need for treatment with intravenous or oral tetracycline derivative antibiotics for an increase in pulmonary symptoms during the 24 week period.
- The proportion of patients requiring intravenous antibiotics during the 24 week period.
- The number of days of treatment with intravenous antibiotics given during the 24 week period.
- The proportion of patients hospitalized.
- The number of hospital days as calculated by calendar days during the 24 week period.
- The proportion of patients requiring oral antibiotics during the 24 week period.
- The number of days of treatment with oral non-tetracycline derivative antibiotics given during the 24 week period.
- Changes in body weight from baseline to completion of the 24 week treatment period.
- Change in level of inflammation as measured by the change in serum CRP and ESR from baseline to the end of the 24 week treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Active comparator | Drug: Azithromycinparticipants taking 500 mg tablets orally thrice weekly for 24 weeks |
| Placebo | Placebo comparator | Drug: PlaceboParticipants taking 500 mg tablets orally thrice weekly for 24 weeks |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Informed consent and verbal assent as appropriate has been provided by the subject
- Ability to comply with medication use, study visits and study procedures as judged by the site Investigator
- Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
- > 18 years of age
- Body weight > 40 kg
Key exclusion criteria (16 listed)
- History of chronic macrolide use, defined as regular macrolide antibiotic use within a three month period prior to enrollment in the study.
- AST or ALT > 2.5 times the upper limit of normal performed at the local laboratories on two occasions prior to randomization.
- Investigational drug use within 30 days of screening
- History of alcohol, illicit drug or medication abuse within 1 year of screening
- Use of intravenous antibiotics or oral antibiotics within 14 days of screening.
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 |
|---|---|---|
| Azithromycin500 mg tablets orally thrice weekly for 24 weeks | Drug | Azithromycin |
| Placebotablet orally thrice weekly for 24 weeks | Drug | Placebo |
Primary outcome
Change in FEV1 in % predicted in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo.
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2009.
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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.
Elizabeth Tullis, MD principal investigator
University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azithromycin in people with Cystic Fibrosis, run by Unity Health Toronto at 1 site 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 10 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 31 Jul 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
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?
Change in FEV1 in % predicted in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo. (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jul 2009.