TEACH: Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)

• Sponsor: Seattle Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02677701
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Cystic Fibrosis Foundation (Other), CF Therapeutics Development Network Coordinating Center (Other)
• Enrollment: 119
• Locations: 39
• Arms: 2
• Actual Duration (Months): 39.8
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a study to examine the effect of combining chronic oral azithromycin with inhaled tobramycin in adolescent and adult subjects with cystic fibrosis who are chronically infected with P. aeruginosa.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: azithromycin; Drug: placebo (for azithromycin); Drug: inhaled tobramycin	Phase 4

Detailed Description

This study is a prospective, randomized, double-blinded, placebo-controlled trial of azithromycin 500mg taken orally thrice weekly vs. placebo in subjects with cystic fibrosis and chronic airway infection with P. aeruginosa who are utilizing chronic inhaled tobramycin therapy. It will include approximately 120 subjects able to complete a primary 6-week study phase. Subjects will be at least 12 years old with a baseline forced expiratory volume at one second (FEV1) between 25-100% predicted. Subjects will continue to use clinically prescribed inhaled tobramycin cycled on/off every 4 weeks. They will be provided over-encapsulated azithromycin 500mg tablets or placebo during the primary study phase. An optional extension phase will be offered to all subjects completing the primary 6-week study. This 8-week extension phase will include an initial 4 weeks without use of inhaled tobramycin or other inhaled antibiotics, followed by a 4-week period with inhaled tobramycin use. All subjects participating in the extension phase of the study will be provided azithromycin 500mg tablets to be taken thrice weekly for the entire 8-week period.

This study will investigate how use of chronic oral azithromycin affects some of the previously demonstrated benefits to health when using inhaled tobramycin. The primary measurements will focus on lung function. Additional measurements will focus on disease-related quality of life as reported by subjects in the trial. Exploratory outcomes, including measurements of safety, are also planned.

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: TEACH Trial: Testing the Effect of Adding CHronic Azithromycin to Inhaled Tobramycin. A Randomized, Placebo-controlled, Double-blinded Trial of Azithromycin 500mg Thrice Weekly in Combination With Inhaled Tobramycin
• Actual Study Start Date: Oct 21, 2016
• Actual Primary Completion Date: Feb 13, 2020
• Actual Study Completion Date: Feb 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: azithromycin azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks	Drug: azithromycin; 500mg tablet over-encapsulated to match placebo; Other Names: Zithromax ; Drug: inhaled tobramycin; clinically prescribed inhaled tobramycin used by subjects participating in the study
Placebo Comparator: placebo encapsulated placebo taken by mouth thrice weekly for 6 weeks	Drug: placebo (for azithromycin); Drug: inhaled tobramycin; clinically prescribed inhaled tobramycin used by subjects participating in the study

Outcome Measures

Primary Outcome Measures

1. Relative Change in Lung Function [baseline (week 0) to week 6 (6 week period)]

   Relative change in FEV1 volume (L) from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6

Secondary Outcome Measures

1. Relative Change in Lung Function [week 2 to week 6 (4 week period)]

   Relative change in FEV1 (L) from the beginning of the 4-week period with inhaled tobramycin at week 2 to the end of the 4-week period with inhaled tobramycin at week 6

2. Change in Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) [baseline (week 0) to week 6 (6 week period)]

   Absolute change in CFRSD-CRISS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. The Cystic Fibrosis Respiratory Symptoms Diary asks a participant to state the extent of 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest, and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present "a great deal" or "extremely." A summed score (ranging from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where lower scores indicate improvement of symptoms.

3. Change in Cystic Fibrosis Questionnaire - Revised Respiratory Symptom Score (CFQ-R RSS) [baseline (week 0) to week 6 (6 week period)]

   Absolute change in the CFQ-R RSS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Age appropriate versions of Cystic Fibrosis Questionnaire - Revised ask a participant from 4 to 6 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] ≥ [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms.

Other Outcome Measures

1. Change in Sputum Pseudomonas Aeruginosa Bacterial Density [baseline (week 0) to week 6 (6 week period)]

   Absolute change in log10 transformed quantitative Pseudomonas aeruginosa (Pa) bacterial density as measured by colony forming units (CFUs) per mL of sputum from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Culture results below the lower limit of detection of 1x10^2 were set to 1/2 of that LLD prior to log transformation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 12 years old or older

• documented diagnosis of cystic fibrosis

• written informed consent (and assent when applicable)

• at least two respiratory cultures growing P. aeruginosa within the last 12 months

• FEV1% predicted between 25-100%

• use of at least two cycles of inhaled tobramycin within the last 24 weeks

• Off TISP and other inhaled anti-pseudomonal antibiotics for at least 2 weeks at Visit 1 and remain off of any inhaled antibiotics for an additional 2 weeks before starting inhaled tobramycin

• most recent liver function test results less than 4 times the upper limit of normal, obtained within the last 12 months

• prior or current use of azithromycin for at least four consecutive weeks

• stable clinical status and therapeutic regimen

Exclusion Criteria:

• weight <40 kg

• positive pregnancy test, lactating, or unwillingness to practice a pre-defined form of contraception, which includes abstinence

• inability to perform reproducible spirometry

• inability or unwillingness to cycle off of inhaled tobramycin for one 4-week period and without use of any additional inhaled antibiotics

• respiratory culture with Burkholderia cepacia complex species within 24 months or with nontuberculous mycobacteria within 18 months of screening

• use of intravenous or oral anti-pseudomonal antibiotics within 4 weeks of screening

• use of investigational therapy within 4 weeks of screening

• use of systemic corticosteroids equivalent to a daily dose more than 10mg of prednisone

• use of nelfinavir, warfarin, haloperidol, or methadone (concern of drug interaction with azithromycin)

• initiation of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy within 30 days

• ECG abnormality at screening requiring prompt further medical attention, or QTc interval >480 msec for males and >486 msec for females

• any other condition that, in the opinion of the site investigator, would compromise the safety of the subject or quality of the data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
2	Stanford University Medical Center	Palo Alto	California	United States	94025
3	Rady Children's Hospital and Health Center at the University of California San Diego	San Diego	California	United States	92123
4	National Jewish Health	Denver	Colorado	United States	80206
5	Yale University School of Medicine	New Haven	Connecticut	United States	06520
6	University of Florida	Gainesville	Florida	United States	32610
7	The Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
8	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
9	Saint Luke's Cystic Fibrosis Center of Idaho	Boise	Idaho	United States	83712
10	Northwestern University	Chicago	Illinois	United States	60208
11	Saint Francis Medical Center	Peoria	Illinois	United States	61637
12	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
13	Maine Medical Partners Pediatric Specialty Care	Portland	Maine	United States	04102
14	Johns Hopkins University	Baltimore	Maryland	United States	21287
15	Boston Children's Hospital	Boston	Massachusetts	United States	02115
16	University of Massachusetts Memorial Health Care	Worcester	Massachusetts	United States	01655
17	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
18	Helen DeVos Children's Hospital	Grand Rapids	Michigan	United States	49503
19	The Minnesota Cystic Fibrosis Center	Minneapolis	Minnesota	United States	55455
20	Children's Mercy Kansas City	Kansas City	Missouri	United States	64108
21	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
22	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
23	Monmouth Medical Center	Long Branch	New Jersey	United States	07740
24	Beth Israel Medical Center	New York	New York	United States	10003
25	Children's Hospital of New York	New York	New York	United States	10032
26	University of Rochester Medical Center Strong Memorial	Rochester	New York	United States	14642
27	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
28	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
29	University Hospitals Case Medical Center/Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
30	Dayton Children's Hospital	Dayton	Ohio	United States	45404
31	Oregon Health Sciences University	Portland	Oregon	United States	97239
32	Hershey Medical Center Pennsylvania State University	Hershey	Pennsylvania	United States	17033
33	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
34	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
35	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
36	Intermountain Cystic Fibrosis Center	Salt Lake City	Utah	United States	84113
37	Seattle Children's Hospital	Seattle	Washington	United States	98145
38	University of Washington Medical Center	Seattle	Washington	United States	98195
39	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Seattle Children's Hospital
• National Heart, Lung, and Blood Institute (NHLBI)
• Cystic Fibrosis Foundation
• CF Therapeutics Development Network Coordinating Center

Investigators

• Principal Investigator: David P Nichols, MD, National Jewish Health

Study Documents (Full-Text)

• Study Protocol - Jun 11, 2018
• Statistical Analysis Plan - Feb 1, 2017

More Information

Publications

None provided.

• Responsible Party: David Nichols, MD, Associate Professor of Pediatrics, Seattle Children's Hospital
• ClinicalTrials.gov Identifier: NCT02677701
• Other Study ID Numbers: TEACH-IP-15; 1R01HL124053-01A1; NICHOL15A0
• First Posted: Feb 9, 2016
• Last Update Posted: Jun 28, 2021
• Last Verified: Jun 1, 2021

• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Azithromycin; Tobramycin

Study Results

Participant Flow

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study	encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study
Period Title: Overall Study
STARTED	62	57
Treated	61	54
COMPLETED	56	52
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Azithromycin	Placebo	Total
Arm/Group Description	azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study	encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study	Total of all reporting groups
Overall Participants	61	54	115
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.1 (9.9)	26.5 (9.7)	26.3 (9.8)
Age, Customized (Count of Participants)
≥ 12 to < 18 years	14 23%	12 22.2%	26 22.6%
≥ 18 to < 30 years	28 45.9%	25 46.3%	53 46.1%
≥ 30 years	19 31.1%	17 31.5%	36 31.3%
Sex: Female, Male (Count of Participants)
Female	29 47.5%	26 48.1%	55 47.8%
Male	32 52.5%	28 51.9%	60 52.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 14.8%	7 13%	16 13.9%
Not Hispanic or Latino	52 85.2%	47 87%	99 86.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.6%	1 1.9%	2 1.7%
Native Hawaiian or Other Pacific Islander	1 1.6%	0 0%	1 0.9%
Black or African American	0 0%	0 0%	0 0%
White	55 90.2%	49 90.7%	104 90.4%
More than one race	3 4.9%	4 7.4%	7 6.1%
Unknown or Not Reported	1 1.6%	0 0%	1 0.9%
Region of Enrollment (participants) [Number]
United States	61 100%	54 100%	115 100%
Cystic Fibrosis (CF) Genotype (Count of Participants)
Delta F508 Homozygous	38 62.3%	35 64.8%	73 63.5%
Delta F508 Heterozygous	17 27.9%	11 20.4%	28 24.3%
Other	6 9.8%	7 13%	13 11.3%
Unidentified	0 0%	0 0%	0 0%
Not Available	0 0%	1 1.9%	1 0.9%
FEV1 (liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters]	2.59 (0.81)	2.50 (0.85)	2.55 (0.83)
ppFEV1 Category (Count of Participants)
≥ 25% to < 50%	11 18%	11 20.4%	22 19.1%
≥ 50% to < 75%	22 36.1%	16 29.6%	38 33%
≥ 75%	28 45.9%	27 50%	55 47.8%
Current Tobramycin Formulation (Count of Participants)
Tobramycin Inhaled Solution	33 54.1%	28 51.9%	61 53%
Tobramycin Inhaled Powder	28 45.9%	26 48.1%	54 47%
History of Azithromycin Use at Baseline (Count of Participants)
Current User	51 83.6%	43 79.6%	94 81.7%
Non-Current User	10 16.4%	11 20.4%	21 18.3%

Outcome Measures

1. Primary Outcome

Title	Relative Change in Lung Function
Description	Relative change in FEV1 volume (L) from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6
Time Frame	baseline (week 0) to week 6 (6 week period)

Outcome Measure Data

Analysis Population Description

Participants in the m-ITT population with spirometry measurements of FEV1 liters at both baseline (week 0) and week 6.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study	encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study
Measure Participants	56	52
Mean (Standard Deviation) [percent change]	1.69 (10.39)	-1.95 (10.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0846
	Comments
	Method	Regression, Linear
	Comments	Adjusted for baseline: ppFEV1 (25%-50%, >50%-75%, >75%), azithromycin use (current vs. non-current), inhaled tobramycin type (powder vs. solution).
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.44
	Confidence Interval	(2-Sided) 95%; -0.48 to 7.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Relative Change in Lung Function
Description	Relative change in FEV1 (L) from the beginning of the 4-week period with inhaled tobramycin at week 2 to the end of the 4-week period with inhaled tobramycin at week 6
Time Frame	week 2 to week 6 (4 week period)

Outcome Measure Data

Analysis Population Description

Participants in the m-ITT population with spirometry measurements of FEV1 liters at both week 2 and week 6.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study	encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study
Measure Participants	56	52
Mean (Standard Deviation) [percent change]	0.44 (8.86)	-0.91 (11.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	Regression, Linear
	Comments	Adjusted for baseline: ppFEV1 (25%-50%, >50%-75%, >75%), azithromycin use (current vs. non-current), inhaled tobramycin type (powder vs. solution).
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; -2.64 to 5.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)
Description	Absolute change in CFRSD-CRISS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. The Cystic Fibrosis Respiratory Symptoms Diary asks a participant to state the extent of 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest, and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present "a great deal" or "extremely." A summed score (ranging from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where lower scores indicate improvement of symptoms.
Time Frame	baseline (week 0) to week 6 (6 week period)

Outcome Measure Data

Analysis Population Description

Participants in the m-ITT population with CFRSD-CRISS diaries at both baseline (week 0) and week 6.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study	encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study
Measure Participants	56	52
Mean (Standard Deviation) [score on a scale]	-2.3 (11.4)	0.6 (9.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Regression, Linear
	Comments	Adjusted for baseline: ppFEV1 (25%-50%, >50%-75%, >75%), azithromycin use (current vs. non-current), inhaled tobramycin type (powder vs. solution).
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.89
	Confidence Interval	(2-Sided) 95%; -7.01 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in Cystic Fibrosis Questionnaire - Revised Respiratory Symptom Score (CFQ-R RSS)
Description	Absolute change in the CFQ-R RSS from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Age appropriate versions of Cystic Fibrosis Questionnaire - Revised ask a participant from 4 to 6 questions related to respiratory symptoms. The Respiratory Domain Scaled Score is calculated as follows: 100*[sum of {responses-1}] / [{number of responses}*3] only if [number of responses] ≥ [number of possible responses]/2; otherwise the score is set to missing. The scaled score ranges from 0 to 100 and higher scores indicate improvement of symptoms.
Time Frame	baseline (week 0) to week 6 (6 week period)

Outcome Measure Data

Analysis Population Description

Participants in the m-ITT population with CFQ-R respiratory symptom scores at both baseline (week 0) and week 6.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study	encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study
Measure Participants	53	52
Mean (Standard Deviation) [score on a scale]	1.0 (14.0)	-0.5 (12.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments	Adjusted for baseline: ppFEV1 (25%-50%, >50%-75%, >75%), azithromycin use (current vs. non-current), inhaled tobramycin type (powder vs. solution).
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 95%; -3.70 to 6.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Other Pre-specified Outcome

Title	Change in Sputum Pseudomonas Aeruginosa Bacterial Density
Description	Absolute change in log10 transformed quantitative Pseudomonas aeruginosa (Pa) bacterial density as measured by colony forming units (CFUs) per mL of sputum from enrollment at week 0 to the end of the 4-week period with inhaled tobramycin at week 6. Culture results below the lower limit of detection of 1x10^2 were set to 1/2 of that LLD prior to log transformation.
Time Frame	baseline (week 0) to week 6 (6 week period)

Outcome Measure Data

Analysis Population Description

Participants in the m-ITT population with Pseudomonas aeruginosa sputum culture results at both baseline (week 0) and week 6.

Arm/Group Title	Azithromycin	Placebo
Arm/Group Description	azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study	encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study
Measure Participants	29	35
Mean (Standard Deviation) [log10(CFUs/mL)]	0.3 (1.7)	-0.5 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azithromycin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments	Adjusted for baseline: ppFEV1 (25%-50%, >50%-75%, >75%), azithromycin use (current vs. non-current), inhaled tobramycin type (powder vs. solution).
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.03 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	6 weeks
Arm/Group Title	Azithromycin		Placebo
Arm/Group Description	azithromycin 500mg tablet over-encapsulated to match placebo in appearance, taken by mouth thrice weekly for 6 weeks azithromycin: 500mg tablet over-encapsulated to match placebo inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study		encapsulated placebo taken by mouth thrice weekly for 6 weeks placebo (for azithromycin) inhaled tobramycin: clinically prescribed inhaled tobramycin used by subjects participating in the study
All Cause Mortality
	Azithromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/54 (0%)
Serious Adverse Events
	Azithromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/61 (6.6%)		3/54 (5.6%)
Gastrointestinal disorders
Constipation	0/61 (0%)	0	1/54 (1.9%)	1
Nausea	0/61 (0%)	0	1/54 (1.9%)	1
Vomiting	0/61 (0%)	0	1/54 (1.9%)	1
General disorders
Chills	0/61 (0%)	0	1/54 (1.9%)	1
Pyrexia	1/61 (1.6%)	1	1/54 (1.9%)	1
Infections and infestations
Sinusitis	0/61 (0%)	0	1/54 (1.9%)	1
Investigations
Forced expiratory volume decreased	1/61 (1.6%)	1	0/54 (0%)	0
Weight decreased	0/61 (0%)	0	1/54 (1.9%)	1
Metabolism and nutrition disorders
Decreased appetite	1/61 (1.6%)	1	0/54 (0%)	0
Reproductive system and breast disorders
Testicular torsion	1/61 (1.6%)	1	0/54 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	2/61 (3.3%)	2	1/54 (1.9%)	1
Dyspnoea	2/61 (3.3%)	2	1/54 (1.9%)	1
Haemoptysis	0/61 (0%)	0	1/54 (1.9%)	1
Productive cough	1/61 (1.6%)	1	0/54 (0%)	0
Respiratory tract congestion	0/61 (0%)	0	1/54 (1.9%)	1
Sputum increased	1/61 (1.6%)	1	1/54 (1.9%)	1
Skin and subcutaneous tissue disorders
Night sweats	0/61 (0%)	0	1/54 (1.9%)	1
Vascular disorders
Deep vein thrombosis	0/61 (0%)	0	1/54 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Azithromycin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/61 (36.1%)		32/54 (59.3%)
Nervous system disorders
Headache	8/61 (13.1%)	15	8/54 (14.8%)	11
Respiratory, thoracic and mediastinal disorders
Cough	12/61 (19.7%)	12	16/54 (29.6%)	17
Dyspnoea	1/61 (1.6%)	1	4/54 (7.4%)	4
Haemoptysis	1/61 (1.6%)	1	4/54 (7.4%)	6
Nasal congestion	3/61 (4.9%)	3	7/54 (13%)	8
Oropharyngeal pain	2/61 (3.3%)	2	4/54 (7.4%)	4
Respiratory tract congestion	2/61 (3.3%)	2	7/54 (13%)	8
Sputum increased	3/61 (4.9%)	3	4/54 (7.4%)	4
Wheezing	0/61 (0%)	0	4/54 (7.4%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.