Ignite Creation Date:
2024-05-05 @ 4:40 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00298922
Status:
UNKNOWN
Last Update Posted:
2009-07-31
First Post:
2006-03-02
Brief Title:
Azithromycin in Patients With CF Infected With Burkholderia Cepacia Complex
Sponsor:
Unity Health Toronto
Organization:
Unity Health Toronto
Study Overview
Official Title:
Phase II Randomized Double Blind Placebo-Controlled Trial of Azithromycin in Patients With CF Chronically Infected With Burkholderia Cepacia Complex
Status:
UNKNOWN
Status Verified Date:
2009-07
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
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 by86 i Emergent B cenocepacia genomovar III ii Emergent non-B cenocepacia genomovars iii Emergent NTM87 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 andor 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
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 by86 i Emergent B cenocepacia genomovar III ii Emergent non-B cenocepacia genomovars iii Emergent NTM87 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 andor 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| TULLIS04A0 | None | None | None |