Trial Outcomes & Findings for Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF) (NCT NCT02677701)
NCT ID: NCT02677701
Last Updated: 2021-06-28
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
119 participants
Primary outcome timeframe
baseline (week 0) to week 6 (6 week period)
Results posted on
2021-06-28
Participant Flow
Participant milestones
| Measure |
Azithromycin
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
|
Placebo
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
|
|---|---|---|
|
Overall Study
STARTED
|
62
|
57
|
|
Overall Study
Treated
|
61
|
54
|
|
Overall Study
COMPLETED
|
56
|
52
|
|
Overall Study
NOT COMPLETED
|
6
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Testing the Effect of Adding Chronic Oral Azithromycin to Inhaled Tobramycin in People With Cystic Fibrosis (CF)
Baseline characteristics by cohort
| Measure |
Azithromycin
n=61 Participants
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
|
Placebo
n=54 Participants
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
n=115 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
26.1 years
STANDARD_DEVIATION 9.9 • n=93 Participants
|
26.5 years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
26.3 years
STANDARD_DEVIATION 9.8 • n=27 Participants
|
|
Age, Customized
Age Distribution · ≥ 12 to < 18 years
|
14 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Age, Customized
Age Distribution · ≥ 18 to < 30 years
|
28 Participants
n=93 Participants
|
25 Participants
n=4 Participants
|
53 Participants
n=27 Participants
|
|
Age, Customized
Age Distribution · ≥ 30 years
|
19 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
36 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
55 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
60 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
52 Participants
n=93 Participants
|
47 Participants
n=4 Participants
|
99 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
55 Participants
n=93 Participants
|
49 Participants
n=4 Participants
|
104 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
61 participants
n=93 Participants
|
54 participants
n=4 Participants
|
115 participants
n=27 Participants
|
|
Cystic Fibrosis (CF) Genotype
Delta F508 Homozygous
|
38 Participants
n=93 Participants
|
35 Participants
n=4 Participants
|
73 Participants
n=27 Participants
|
|
Cystic Fibrosis (CF) Genotype
Delta F508 Heterozygous
|
17 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
28 Participants
n=27 Participants
|
|
Cystic Fibrosis (CF) Genotype
Other
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
|
Cystic Fibrosis (CF) Genotype
Unidentified
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Cystic Fibrosis (CF) Genotype
Not Available
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
FEV1
|
2.59 liters
STANDARD_DEVIATION 0.81 • n=93 Participants
|
2.50 liters
STANDARD_DEVIATION 0.85 • n=4 Participants
|
2.55 liters
STANDARD_DEVIATION 0.83 • n=27 Participants
|
|
ppFEV1 Category
≥ 25% to < 50%
|
11 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
|
ppFEV1 Category
≥ 50% to < 75%
|
22 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
38 Participants
n=27 Participants
|
|
ppFEV1 Category
≥ 75%
|
28 Participants
n=93 Participants
|
27 Participants
n=4 Participants
|
55 Participants
n=27 Participants
|
|
Current Tobramycin Formulation
Tobramycin Inhaled Solution
|
33 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
61 Participants
n=27 Participants
|
|
Current Tobramycin Formulation
Tobramycin Inhaled Powder
|
28 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
54 Participants
n=27 Participants
|
|
History of Azithromycin Use at Baseline
Current User
|
51 Participants
n=93 Participants
|
43 Participants
n=4 Participants
|
94 Participants
n=27 Participants
|
|
History of Azithromycin Use at Baseline
Non-Current User
|
10 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: baseline (week 0) to week 6 (6 week period)Population: Participants in the m-ITT population with spirometry measurements of FEV1 liters at both baseline (week 0) and week 6.
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
Outcome measures
| Measure |
Azithromycin
n=56 Participants
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
|
Placebo
n=52 Participants
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
|
|---|---|---|
|
Relative Change in Lung Function
|
1.69 percent change
Standard Deviation 10.39
|
-1.95 percent change
Standard Deviation 10.73
|
SECONDARY outcome
Timeframe: week 2 to week 6 (4 week period)Population: Participants in the m-ITT population with spirometry measurements of FEV1 liters at both week 2 and week 6.
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
Outcome measures
| Measure |
Azithromycin
n=56 Participants
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
|
Placebo
n=52 Participants
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
|
|---|---|---|
|
Relative Change in Lung Function
|
0.44 percent change
Standard Deviation 8.86
|
-0.91 percent change
Standard Deviation 11.41
|
SECONDARY outcome
Timeframe: baseline (week 0) to week 6 (6 week period)Population: Participants in the m-ITT population with CFRSD-CRISS diaries at both baseline (week 0) and week 6.
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.
Outcome measures
| Measure |
Azithromycin
n=56 Participants
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
|
Placebo
n=52 Participants
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
|
|---|---|---|
|
Change in Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)
|
-2.3 score on a scale
Standard Deviation 11.4
|
0.6 score on a scale
Standard Deviation 9.8
|
SECONDARY outcome
Timeframe: baseline (week 0) to week 6 (6 week period)Population: Participants in the m-ITT population with CFQ-R respiratory symptom scores at both baseline (week 0) and week 6.
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.
Outcome measures
| Measure |
Azithromycin
n=53 Participants
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
|
Placebo
n=52 Participants
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
|
|---|---|---|
|
Change in Cystic Fibrosis Questionnaire - Revised Respiratory Symptom Score (CFQ-R RSS)
|
1.0 score on a scale
Standard Deviation 14.0
|
-0.5 score on a scale
Standard Deviation 12.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline (week 0) to week 6 (6 week period)Population: Participants in the m-ITT population with Pseudomonas aeruginosa sputum culture results at both baseline (week 0) and week 6.
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.
Outcome measures
| Measure |
Azithromycin
n=29 Participants
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
|
Placebo
n=35 Participants
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
|
|---|---|---|
|
Change in Sputum Pseudomonas Aeruginosa Bacterial Density
|
0.3 log10(CFUs/mL)
Standard Deviation 1.7
|
-0.5 log10(CFUs/mL)
Standard Deviation 1.2
|
Adverse Events
Azithromycin
Serious events: 4 serious events
Other events: 22 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Azithromycin
n=61 participants at risk
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
|
Placebo
n=54 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
General disorders
Chills
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
General disorders
Pyrexia
|
1.6%
1/61 • Number of events 1 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Infections and infestations
Sinusitis
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Investigations
Forced expiratory volume decreased
|
1.6%
1/61 • Number of events 1 • 6 weeks
|
0.00%
0/54 • 6 weeks
|
|
Investigations
Weight decreased
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.6%
1/61 • Number of events 1 • 6 weeks
|
0.00%
0/54 • 6 weeks
|
|
Reproductive system and breast disorders
Testicular torsion
|
1.6%
1/61 • Number of events 1 • 6 weeks
|
0.00%
0/54 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.3%
2/61 • Number of events 2 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.3%
2/61 • Number of events 2 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
1.6%
1/61 • Number of events 1 • 6 weeks
|
0.00%
0/54 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
1.6%
1/61 • Number of events 1 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/61 • 6 weeks
|
1.9%
1/54 • Number of events 1 • 6 weeks
|
Other adverse events
| Measure |
Azithromycin
n=61 participants at risk
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
|
Placebo
n=54 participants at risk
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
|
|---|---|---|
|
Nervous system disorders
Headache
|
13.1%
8/61 • Number of events 15 • 6 weeks
|
14.8%
8/54 • Number of events 11 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.7%
12/61 • Number of events 12 • 6 weeks
|
29.6%
16/54 • Number of events 17 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.6%
1/61 • Number of events 1 • 6 weeks
|
7.4%
4/54 • Number of events 4 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.6%
1/61 • Number of events 1 • 6 weeks
|
7.4%
4/54 • Number of events 6 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.9%
3/61 • Number of events 3 • 6 weeks
|
13.0%
7/54 • Number of events 8 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
3.3%
2/61 • Number of events 2 • 6 weeks
|
7.4%
4/54 • Number of events 4 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
3.3%
2/61 • Number of events 2 • 6 weeks
|
13.0%
7/54 • Number of events 8 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
4.9%
3/61 • Number of events 3 • 6 weeks
|
7.4%
4/54 • Number of events 4 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/61 • 6 weeks
|
7.4%
4/54 • Number of events 4 • 6 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place