Cystic FibrosisPhase 4NCT00431964
Effect of Azithromycin on Lung Function in 6-18 Year-olds With Cystic Fibrosis (CF) Not Infected With P. Aeruginosa
A Phase 4 study testing azithromycin 250 mg tablets in people with Cystic Fibrosis, run by CF Therapeutics Development Network Coordinating Center at 40 sites in 2 countries.
Trial summary
This is a study to examine the safety, effect on lung function, and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin in 6-18 year-olds with CF who are not infected with Pseudomonas aeruginosa. Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- azithromycin 250 mg tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 263 participants
- Where
- 40 sitesin 2 countries
- Study dates
- Feb 2007to Nov 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male or female, 6-18 years of age at enrollment
- Confirmed diagnosis of CF
- Written informed consent (and assent when applicable)
- Clinically stable at enrollment as assessed by the site investigator
- FEV1 % predicted > 50%
- Ability to comply with medication use, study visits, and study procedures
- Ability to swallow a 250 mg tablet
Who cannot join
- Weight less than 18.0 kg
- Respiratory culture positive for P. aeruginosa, NTM, or B. cepacia complex within 1 year or at screening, or AFB positive at screening
- Allergy to macrolide antibiotics
- Use of macrolide antibiotics (e.g., azithromycin, clarithromycin) within 60 days of screening
- Use of systemic corticosteroids or intravenous or oral antibiotics within 14 days of screening
- Initiation of high dose ibuprofen, Pulmozyme®, hypertonic saline or aerosolized antibiotics within 30 days of screening
Show all 18Show fewer
- Chronic therapy with drugs known to have rare but serious interactions with azithromycin: amiodarone, digoxin, disopyramide, lovastatin, pimozide, rifabutin, and nelfinavir
- Investigational drug use within 30 days of screening
- Laboratory abnormalities (creatinine, liver function or neutropenia) at screening and confirmed at follow-up testing prior to randomization
- History of biliary cirrhosis, portal hypertension, or splenomegaly, or splenomegaly on physical exam
- History of ventricular arrhythmia
- Other major organ dysfunction, excluding pancreatic dysfunction
- History of lung transplantation or currently on lung transplant list
- Relative decrease in FEV1 % predicted ≥ 20% between the screening and enrollment visit
- Positive serum pregnancy test at screening
- Pregnant, breastfeeding, or if post-menarche female, unwilling to practice birth control during participation in the study
- History of alcohol, illicit drug or medication abuse within 1 year of screening in the judgment of the site investigator
- Presence of a condition or abnormality that in the opinion of the site investigator would compromise the safety of the subject or the quality of the data
Trial locations and contacts
40 sites in 2 countries.
40 sites in 2 countries
United States31 sites
University of Michigan
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
Children's Hospital Boston
Boston, Massachusetts, 02115
Vermont Children's Hospital
Burlington, Vermont, 05401
UNC Chapel Hill
Chapel Hill, North Carolina, 27599
University of Virginia at Charlottesville Children's Hospital
Charlottesville, Virginia, 22908
Children's Memorial Hospital
Chicago, Illinois, 60614
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Riley Hospital for Children
Indianapolis, Indiana, 46202
Children's Mercy Hospital
Kansas City, Missouri, 64108
East Tennessee Children's Hospital, Pediatric Pulmonary & Respiratory Care
Knoxville, Tennessee, 37916
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Kentucky
Lexington, Kentucky, 40536
University of Tennessee Health Science Center
Memphis, Tennessee, 38105
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota
Minneapolis, Minnesota, 55455
West Virginia University
Morgantown, West Virginia, 26506
Vanderbilt Children's Hospital
Nashville, Tennessee, 37232
Columbia University
New York, New York, 10032
University of Nebraska Medical Center - Pediatric Pulmonary
Omaha, Nebraska, 68198
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh, Pulmonary Medicine, Allergy & Immunology
Pittsburgh, Pennsylvania, 15213
University of Rochester Medical Center
Rochester, New York, 14642
University of Utah Pediatric Pulmonology
Salt Lake City, Utah, 84108
Washington University
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210
New York Medical College
Valhalla, New York, 10595
Canada9 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
CSSS de Chicoutimi
Chicoutimi, Quebec, G7H 5H6
McMaster Health Sciences Centre
Hamilton, Ontario, L8N 3Z5
Bryan Lyttle, MD, Private Practice
London, Ontario, N6A 5B8
Montreal Children's Hospital
Montreal, Quebec, H3H 1P3
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Janeway Children's Health & Rehabilitation Hospital
St. John's, Newfoundland and Labrador, A1B 3V6
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
BC Children's Hospital
Vancouver, British Columbia, V6H 3V4
About this study
Official title: Multi-center, Multi-national, Randomized, Placebo-Controlled Trial of Azithromycin in Subjects With Cystic Fibrosis 6-18 Years Old, Culture Negative for Pseudomonas Aeruginosa
This is a study to examine the safety, effect on lung function, and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin in 6-18 year-olds with CF who are not infected with Pseudomonas aeruginosa.
Read the detailed description
Azithromycin is an antibiotic that has been shown to improve lung function in patients with cystic fibrosis (CF) whose lungs are infected with a bacterium called Pseudomonas aeruginosa. Scientists are not sure how azithromycin works in cystic fibrosis. It does not appear to work by killing the bacteria Pseudomonas aeruginosa, but it may make these bacteria and other bacteria less damaging to the lungs by reducing their ability to attach to the lining of the lung, or by reducing the bacteria's ability to make substances that damage the lungs of patients with cystic fibrosis. Azithromycin may also work directly on the cells in the lungs to improve lung function. This could occur by reducing inflammation (swelling) in the lungs, and/or making the mucus less sticky, or by affecting the salt channel that doesn't function correctly in CF. If azithromycin works in one or more of these ways; it may also be effective in improving lung function in cystic fibrosis patients who are not infected with Pseudomonas aeruginosa.
We are conducting this research study to examine the safety, effect on lung function and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin. This study is designed to determine if patients with cystic fibrosis whose lungs are not infected with the bacteria Pseudomonas aeruginosa will benefit from 24 weeks of treatment with the antibiotic azithromycin. Benefit will be determined as having better pulmonary function tests and getting sick less often compared to a placebo (sugar pill). This study is also designed to determine if azithromycin is safe when administered for 24 weeks to cystic fibrosis patients not infected with Pseudomonas aeruginosa. By doing this study, we hope to learn more about CF and improve the way in which we treat it.
Comparison: Three times weekly azithromycin tablets added to standard care, compared to three times weekly placebo tablets added to standard care.
- Conditions
- Cystic Fibrosis
- Being tested
- azithromycin 250 mg tablets, placebo tablets
- Keywords
- azithromycin, Zithromax
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
azithromycin 250 mg tabletsDrug
Also called Zithromax
- One (1) tablet three times weekly for patients who weigh 40-79 lbs
- Two (2) tablets three times weekly for patients who weigh greater than or equal to 80 lbs
placebo tabletsDrug
Also called inactive pill
- One (1) tablet three times weekly for patients who weigh 40-79 lbs
- Two (2) tablets three times weekly for patients who weigh greater than or equal to 80 lbs
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | azithromycin 250 mg tablets Receives: Drug: azithromycin 250 mg tablets |
| Placebo | Placebo comparator | placebo tablets (matched to active drug in appearance) Receives: Drug: placebo tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in FEV1 From Baseline to End of Treatment at Day 168
Measured: change from baseline to day 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2007 (estimated)
- Study startFeb 2007
- Primary completionJul 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 263 participants (actual)
Sponsor and investigators
- Lead sponsor
- CF Therapeutics Development Network Coordinating Center
- Sponsor type
- Research network
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Sponsor
- Investigators
- Lisa Saiman, MD, MPH, Principal investigator, Columbia UniversityMichael Anstead, MD, Principal investigator, University of KentuckyFelix Ratjen, MD, Principal investigator, The Hospital for Sick Children, Toronto, OntarioLarry Lands, MD, Principal investigator, Montreal Children's Hospital of the MUHC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00431964
- Sponsor's protocol ID
- AZ0004
- Status last verified
- Jul 2015
- First submitted
- 2 Feb 2007
- Last updated
- 19 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Saiman L, Anstead M, Mayer-Hamblett N, Lands LC, Kloster M, Hocevar-Trnka J, Goss CH, Rose LM, Burns JL, Marshall BC, Ratjen F; AZ0004 Azithromycin Study Group. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2010 May 5;303(17):1707-15. doi: 10.1001/jama.2010.563.
PubMed 20442386Ratjen F, Saiman L, Mayer-Hamblett N, Lands LC, Kloster M, Thompson V, Emmett P, Marshall B, Accurso F, Sagel S, Anstead M. Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa. Chest. 2012 Nov;142(5):1259-1266. doi: 10.1378/chest.12-0628.
PubMed 22595153
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center, Multi-national, Randomized, Placebo-Controlled Trial of Azithromycin in Subjects With Cystic Fibrosis 6-18 Years Old, Culture Negative for Pseudomonas Aeruginosa
- ClinicalTrials.gov ID
- NCT00431964
- Acronym / sponsor ID
- AZ0004
- Conditions
- Cystic Fibrosis
- Keywords
- azithromycin, Zithromax
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 263 participants (actual)
- Lead sponsor
- CF Therapeutics Development Network Coordinating CenterResearch network
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- Feb 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 6 Feb 2007 (estimated)
- Results
- Posted 19 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to examine the safety, effect on lung function, and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin in 6-18 year-olds with CF who are not infected with Pseudomonas aeruginosa.
Detailed description
Azithromycin is an antibiotic that has been shown to improve lung function in patients with cystic fibrosis (CF) whose lungs are infected with a bacterium called Pseudomonas aeruginosa. Scientists are not sure how azithromycin works in cystic fibrosis. It does not appear to work by killing the bacteria Pseudomonas aeruginosa, but it may make these bacteria and other bacteria less damaging to the lungs by reducing their ability to attach to the lining of the lung, or by reducing the bacteria's ability to make substances that damage the lungs of patients with cystic fibrosis. Azithromycin may also work directly on the cells in the lungs to improve lung function. This could occur by reducing inflammation (swelling) in the lungs, and/or making the mucus less sticky, or by affecting the salt channel that doesn't function correctly in CF. If azithromycin works in one or more of these ways; it may also be effective in improving lung function in cystic fibrosis patients who are not infected with Pseudomonas aeruginosa.
We are conducting this research study to examine the safety, effect on lung function and frequency of symptoms relating to cystic fibrosis during 24 weeks of treatment with the antibiotic azithromycin. This study is designed to determine if patients with cystic fibrosis whose lungs are not infected with the bacteria Pseudomonas aeruginosa will benefit from 24 weeks of treatment with the antibiotic azithromycin. Benefit will be determined as having better pulmonary function tests and getting sick less often compared to a placebo (sugar pill). This study is also designed to determine if azithromycin is safe when administered for 24 weeks to cystic fibrosis patients not infected with Pseudomonas aeruginosa. By doing this study, we hope to learn more about CF and improve the way in which we treat it.
Comparison: Three times weekly azithromycin tablets added to standard care, compared to three times weekly placebo tablets added to standard care.
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 |
|---|---|---|
| Active | Active comparator | Drug: azithromycin 250 mg tabletsazithromycin 250 mg tablets |
| Placebo | Placebo comparator | Drug: placebo tabletsplacebo tablets (matched to active drug in appearance) |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Male or female, 6-18 years of age at enrollment
- Confirmed diagnosis of CF
- Written informed consent (and assent when applicable)
- Clinically stable at enrollment as assessed by the site investigator
- FEV1 % predicted > 50%
Key exclusion criteria (18 listed)
- Weight less than 18.0 kg
- Respiratory culture positive for P. aeruginosa, NTM, or B. cepacia complex within 1 year or at screening, or AFB positive at screening
- Allergy to macrolide antibiotics
- Use of macrolide antibiotics (e.g., azithromycin, clarithromycin) within 60 days of screening
- Use of systemic corticosteroids or intravenous 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 |
|---|---|---|
| azithromycin 250 mg tabletsAlso: Zithromax* One (1) tablet three times weekly for patients who weigh 40-79 lbs * Two (2) tablets three times weekly for patients who weigh greater than or equal to 80 lbs | Drug | Active |
| placebo tabletsAlso: inactive pill* One (1) tablet three times weekly for patients who weigh 40-79 lbs * Two (2) tablets three times weekly for patients who weigh greater than or equal to 80 lbs | Drug | Placebo |
Primary outcome
Change in FEV1 From Baseline to End of Treatment at Day 168
Time frame: change from baseline to day 168
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20442386Saiman L, Anstead M, Mayer-Hamblett N, Lands LC, Kloster M, Hocevar-Trnka J, Goss CH, Rose LM, Burns JL, Marshall BC, Ratjen F; AZ0004 Azithromycin Study Group. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2010 May 5;303(17):1707-15. doi: 10.1001/jama.2010.563.
- Derived from this study: PubMed 22595153Ratjen F, Saiman L, Mayer-Hamblett N, Lands LC, Kloster M, Thompson V, Emmett P, Marshall B, Accurso F, Sagel S, Anstead M. Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa. Chest. 2012 Nov;142(5):1259-1266. doi: 10.1378/chest.12-0628.
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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.
Lisa Saiman, MD, MPH principal investigator
Columbia University
Michael Anstead, MD principal investigator
University of Kentucky
Felix Ratjen, MD principal investigator
The Hospital for Sick Children, Toronto, Ontario
40 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing azithromycin 250 mg tablets in people with Cystic Fibrosis, run by CF Therapeutics Development Network Coordinating Center at 40 sites in 2 countries.
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 7 inclusion and 18 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 19 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 From Baseline to End of Treatment at Day 168 (time frame: change from baseline to day 168). 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 NCT00431964, which also lists 2 linked publications.
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 19 Aug 2015.