Trial Outcomes & Findings for Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis (NCT NCT00669331)
NCT ID: NCT00669331
Last Updated: 2016-04-29
Results Overview
A graded pulmonary exacerbation was defined as a worsening in signs and symptoms requiring a change in treatment (Center for Drug Evaluation and Research (CDER), 2007). Grade I was required 3 main signs and symptoms, Grade II 2 main signs and symptoms and Grade III 1 main and one or more minor signs and symptoms. Main signs and symptoms were increased cough, sputum volume or sputum purulence. Minor were upper respiratory tract infection, fever, increased wheezing, increased dyspnea, increase in respiratory rate, increase in cardiac frequency of \>20%, and increased malaise, fatigue or lethargy. Rate is defined as the number of all GPE events observed in one treatment year
COMPLETED
PHASE3
485 participants
52 weeks
2016-04-29
Participant Flow
Prior to randomisation, subjects underwent a Mannitol Tolerance Test (MTT) - only those who passed the MTT were eligible to be randomised. 581 patients in total underwent the MTT
Participant milestones
| Measure |
Mannitol
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Randomisation to First Dose
STARTED
|
244
|
241
|
|
Randomisation to First Dose
COMPLETED
|
233
|
228
|
|
Randomisation to First Dose
NOT COMPLETED
|
11
|
13
|
|
Blinded Treatment Period
STARTED
|
233
|
228
|
|
Blinded Treatment Period
COMPLETED
|
191
|
189
|
|
Blinded Treatment Period
NOT COMPLETED
|
42
|
39
|
Reasons for withdrawal
| Measure |
Mannitol
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Randomisation to First Dose
Adverse Event
|
1
|
0
|
|
Randomisation to First Dose
Protocol Violation
|
1
|
0
|
|
Randomisation to First Dose
Withdrawal by Subject
|
3
|
2
|
|
Randomisation to First Dose
Lost to Follow-up
|
2
|
0
|
|
Randomisation to First Dose
Death
|
1
|
0
|
|
Randomisation to First Dose
Sponsor decision
|
0
|
1
|
|
Randomisation to First Dose
Randomised in error
|
3
|
10
|
|
Blinded Treatment Period
Adverse Event
|
16
|
10
|
|
Blinded Treatment Period
Protocol Violation
|
1
|
1
|
|
Blinded Treatment Period
Withdrawal by Subject
|
17
|
19
|
|
Blinded Treatment Period
Lost to Follow-up
|
3
|
2
|
|
Blinded Treatment Period
Death
|
0
|
2
|
|
Blinded Treatment Period
Physician Decision
|
3
|
3
|
|
Blinded Treatment Period
Unable/unwilling to comply w trial reqs
|
2
|
2
|
Baseline Characteristics
Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis
Baseline characteristics by cohort
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
Total
n=461 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.30 years
STANDARD_DEVIATION 14.06 • n=5 Participants
|
60.26 years
STANDARD_DEVIATION 13.02 • n=7 Participants
|
59.77 years
STANDARD_DEVIATION 13.55 • n=5 Participants
|
|
Sex: Female, Male
Female
|
147 Participants
n=5 Participants
|
142 Participants
n=7 Participants
|
289 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=5 Participants
|
86 Participants
n=7 Participants
|
172 Participants
n=5 Participants
|
|
Baseline Pulmonary Exacerbation rate
|
3.20 events/year
STANDARD_DEVIATION 1.38 • n=5 Participants
|
3.25 events/year
STANDARD_DEVIATION 1.40 • n=7 Participants
|
3.22 events/year
STANDARD_DEVIATION 1.39 • n=5 Participants
|
|
Baseline % of Predicted FEV1
<60%
|
101 participants
n=5 Participants
|
107 participants
n=7 Participants
|
208 participants
n=5 Participants
|
|
Baseline % of Predicted FEV1
>=60%
|
132 participants
n=5 Participants
|
121 participants
n=7 Participants
|
253 participants
n=5 Participants
|
|
Extent of Bronchiectasis
Diffuse
|
133 participants
n=5 Participants
|
118 participants
n=7 Participants
|
251 participants
n=5 Participants
|
|
Extent of Bronchiectasis
Focal
|
77 participants
n=5 Participants
|
73 participants
n=7 Participants
|
150 participants
n=5 Participants
|
|
Extent of Bronchiectasis
Both (Diffuse and Focal)
|
23 participants
n=5 Participants
|
37 participants
n=7 Participants
|
60 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: Randomised and Treated (referred to as the ITT population in this trial)
A graded pulmonary exacerbation was defined as a worsening in signs and symptoms requiring a change in treatment (Center for Drug Evaluation and Research (CDER), 2007). Grade I was required 3 main signs and symptoms, Grade II 2 main signs and symptoms and Grade III 1 main and one or more minor signs and symptoms. Main signs and symptoms were increased cough, sputum volume or sputum purulence. Minor were upper respiratory tract infection, fever, increased wheezing, increased dyspnea, increase in respiratory rate, increase in cardiac frequency of \>20%, and increased malaise, fatigue or lethargy. Rate is defined as the number of all GPE events observed in one treatment year
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Rate of Graded Pulmonary Exacerbations
Raw rate
|
1.95 GPE events per year
|
2.10 GPE events per year
|
|
Rate of Graded Pulmonary Exacerbations
Rate from negative binomial model
|
1.69 GPE events per year
|
1.84 GPE events per year
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Randomised and treated with one or more post-baseline SGRQ data available
The SGRQ was collected at baseline, week 6, week 16, week 28, week 40 and week 52. Change in total score was calculated from baseline. Total scores are a weighted sum across all questions. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. Higher scores indicate lower quality of life. Outcome data table gives the raw mean total score at each visit.
Outcome measures
| Measure |
Mannitol
n=228 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=219 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Quality of Life as Measured by the St. Georges Respiratory Questionnaire (SGRQ) Total Score
Baseline
|
52.98 units on a scale
Standard Deviation 14.64
|
52.22 units on a scale
Standard Deviation 14.71
|
|
Quality of Life as Measured by the St. Georges Respiratory Questionnaire (SGRQ) Total Score
Week 6
|
44.09 units on a scale
Standard Deviation 17.49
|
44.55 units on a scale
Standard Deviation 18.49
|
|
Quality of Life as Measured by the St. Georges Respiratory Questionnaire (SGRQ) Total Score
Week 16
|
40.67 units on a scale
Standard Deviation 19.07
|
44.23 units on a scale
Standard Deviation 19.89
|
|
Quality of Life as Measured by the St. Georges Respiratory Questionnaire (SGRQ) Total Score
Week 28
|
41.45 units on a scale
Standard Deviation 18.58
|
43.46 units on a scale
Standard Deviation 19.05
|
|
Quality of Life as Measured by the St. Georges Respiratory Questionnaire (SGRQ) Total Score
Week 40
|
40.39 units on a scale
Standard Deviation 18.86
|
43.51 units on a scale
Standard Deviation 19.96
|
|
Quality of Life as Measured by the St. Georges Respiratory Questionnaire (SGRQ) Total Score
Week 52
|
41.43 units on a scale
Standard Deviation 19.60
|
42.25 units on a scale
Standard Deviation 19.50
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Randomised and treated (referred to as ITT)
Rate of antibiotic treated graded pulmonary exacerbations, using the same definition of a graded pulmonary exacerbation as the primary endpoint. A graded pulmonary exacerbation was considered to be anti-biotic treated if use of oral, IV or inhaled antibiotic use was recorded related to the GPE event.
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Antibiotic Use Prescribed for Treated Pulmonary Exacerbations
|
1.9 events/year
|
2.1 events/year
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Randomised and treated
Time to first graded exacerbation is defined as the duration (in months) from the randomisation date to the start of the first reported graded PE during the on-treatment period. Patients without reported graded PE event will be censored at the last participation.
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Time to First Graded Exacerbation
|
5.4 months
Interval 4.1 to 6.7
|
4.1 months
Interval 3.5 to 4.7
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Randomised and treated
Duration of graded exacerbations is defined as the number of days with graded PE within one treatment year. Mean days estimated via negative binomial model with treatment, region and baseline pulmonary exacerbation rate as predictors, with log of follow-up time as the offset variable
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Duration of Graded Exacerbations
|
31.49 Days with GPE
Interval 25.54 to 38.82
|
35.74 Days with GPE
Interval 28.9 to 44.2
|
SECONDARY outcome
Timeframe: 52 weeks24 hour sputum weight, measured at baseline, week 6, week 16, week 28, week 40, week 52
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Sputum Volume
Baseline
|
28.88 g
Standard Deviation 18.71
|
28.96 g
Standard Deviation 19.92
|
|
Sputum Volume
Week 6
|
24.97 g
Standard Deviation 23.17
|
22.82 g
Standard Deviation 20.06
|
|
Sputum Volume
Week 16
|
23.69 g
Standard Deviation 22.09
|
20.25 g
Standard Deviation 16.99
|
|
Sputum Volume
Week 28
|
22.92 g
Standard Deviation 25.66
|
18.88 g
Standard Deviation 17.83
|
|
Sputum Volume
Week 40
|
21.56 g
Standard Deviation 21.58
|
18.17 g
Standard Deviation 16.67
|
|
Sputum Volume
Week 52
|
20.54 g
Standard Deviation 24.07
|
18.33 g
Standard Deviation 16.00
|
SECONDARY outcome
Timeframe: 52 weeksEpworth Sleepiness Scale (ESS) score was calculated as the sum of scores for each of eight individual questions, such that a total score of zero represents no daytime sleepiness, and a total score of 24 represents the maximum degree of daytime sleepiness. Measured at baseline, 6 weeks, 16 weeks, 28 weeks, 40 weeks, 52 weeks
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Daytime Sleepiness Scores
Baseline
|
7.23 units on a scale
Standard Deviation 4.85
|
6.89 units on a scale
Standard Deviation 4.89
|
|
Daytime Sleepiness Scores
Week 6
|
6.07 units on a scale
Standard Deviation 4.78
|
6.87 units on a scale
Standard Deviation 4.74
|
|
Daytime Sleepiness Scores
Week 16
|
6.21 units on a scale
Standard Deviation 5.10
|
6.50 units on a scale
Standard Deviation 4.86
|
|
Daytime Sleepiness Scores
Week 28
|
6.05 units on a scale
Standard Deviation 4.73
|
6.57 units on a scale
Standard Deviation 4.82
|
|
Daytime Sleepiness Scores
Week 40
|
6.32 units on a scale
Standard Deviation 5.10
|
6.33 units on a scale
Standard Deviation 4.83
|
|
Daytime Sleepiness Scores
Week 52
|
6.09 units on a scale
Standard Deviation 4.98
|
6.34 units on a scale
Standard Deviation 5.02
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Randomised and treated with at least one post-baseline spirometry assessment
Outcome measures
| Measure |
Mannitol
n=229 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=219 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Lung Function - Change in FEV1 (Forced Expiratory Volume in One Second)
|
2.36 mL
Interval -24.03 to 28.74
|
-5.20 mL
Interval -32.35 to 21.95
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Randomised and treated with at least one post-baseline spirometry assessment
Outcome measures
| Measure |
Mannitol
n=229 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=219 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Lung Function - Change in FVC (Forced Vital Capacity)
|
0.15 mL
Interval -36.75 to 37.05
|
-15.70 mL
Interval -53.64 to 22.25
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Randomised and treated with at least one post-baseline spirometry assessment
FEV1 expressed as a ratio of FVC. Endpoint is expressed as a percentage ie FEV1/FVC\*100
Outcome measures
| Measure |
Mannitol
n=229 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=219 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Lung Function - Change in FEV1/FVC
|
-0.08 ratio (expressed as a %)
Interval -0.68 to 0.53
|
0.09 ratio (expressed as a %)
Interval -0.52 to 0.71
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Randomised and treated with at least one post-baseline spirometry assessment
Outcome measures
| Measure |
Mannitol
n=229 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=219 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Lung Function - Change in FEF25-75 (Forced Expiratory Flow Rate Averaged Over 25th -75th Percentile of FVC)
|
-18.21 mL/s
Interval -59.09 to 22.67
|
-3.40 mL/s
Interval -45.28 to 38.47
|
SECONDARY outcome
Timeframe: 52 weekssputum microbiology assessed as the presence of abnormal flora in sputum sample taken at any post baseline visit
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Safety Profile - Sputum Microbiology
|
81 participants
|
81 participants
|
SECONDARY outcome
Timeframe: 52 weeksClinical chemistry was assessed as clinically significant abnormal liver function test and clinically significant abnormal urea/electrolyte test at any point post baseline.
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=288 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Safety Profile - Clinical Chemistry
Subjects with Clin sig liver funtion tests at wk52
|
2 participants
|
0 participants
|
|
Safety Profile - Clinical Chemistry
Subjects with clin sig urea/electrolyte test wk52
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 52 weekshematology assessed as clinically significant abnormal FBC (Full Blood count) at any point post baseline.
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Safety Profile - Hematology
|
13 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 52 weeksMean rate of hospitalisations (number/year) summarised and analysed to take account of differing follow-up times.
Outcome measures
| Measure |
Mannitol
n=233 Participants
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 Participants
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
• (Exploratory) Number of Hospitalizations Due to Pulmonary Exacerbations
|
0.12 hospitalisations/year
Interval 0.07 to 0.2
|
0.20 hospitalisations/year
Interval 0.13 to 0.31
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 52 weeksPopulation: No data were collected. Since the primary objective was not significant in this study, further exploration of health economic endpoints was not done.
In the presence of a significant primary endpoint, these data were intended to be derived using the trial data together with external information (Note as the primary objective of this study did not reach statistical significance, health related costs were not assessed)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 52 weeksPopulation: No data were collected. As the primary objective of this study did not reach statistical significance, health status and utility scores were not derived.
In the presence of a significant primary endpoint, these data were intended to be derived from the trial data and external information (Note as the primary objective of this study did not reach statistical significance, differences in health status and utility scores were not assessed)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 52 weeksPopulation: No data were collected for this assessment. As the primary objective of this study did not reach statistical significance, HRQL and QALYs were not derived.
In the presence of a significant primary endpoint, these data were intended to be derived using the trial data and external information (Note as the primary objective of this study did not reach statistical significance, HRQL and QALYs were not collected).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 52 weeksPopulation: Not collected. As the primary objective of this study did not reach statistical significance, cost effectiveness data were not collected.
In the presence of a significant primary endpoint, these data were intended to be derived using the trial data and external information (Note as the primary objective of this study did not reach statistical significance, cost effectiveness was not collected).
Outcome measures
Outcome data not reported
Adverse Events
Mannitol
Control
Serious adverse events
| Measure |
Mannitol
n=233 participants at risk
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 participants at risk
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Cardiac disorders
Angina Pectoris
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Cardiac disorders
Cardiac Failure Congestive
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/233 • 52 weeks
|
0.88%
2/228 • 52 weeks
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.43%
1/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
General disorders
Catheter related complication
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
General disorders
Chest pain
|
0.86%
2/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
General disorders
Condition Aggravated
|
9.0%
21/233 • 52 weeks
|
11.4%
26/228 • 52 weeks
|
|
General disorders
Disease prodomal stage
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
General disorders
Multi-organ failure
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Hepatobiliary disorders
Cholecystisis
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Infections and infestations
Appendicitis
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Infections and infestations
Dacryocystisis
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Infections and infestations
Lobar pneumonia
|
0.43%
1/233 • 52 weeks
|
0.88%
2/228 • 52 weeks
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Infections and infestations
Lung abscess
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Infections and infestations
Lung infection pseudomonal
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Infections and infestations
Pneumonia
|
3.0%
7/233 • 52 weeks
|
3.1%
7/228 • 52 weeks
|
|
Infections and infestations
Swine Influenza
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Injury, poisoning and procedural complications
Fibula Fracture
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Injury, poisoning and procedural complications
Seroma
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Injury, poisoning and procedural complications
Skin lacreation
|
0.86%
2/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer metastatic
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Nervous system disorders
Syncope
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Nervous system disorders
Transient global amnesia
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Reproductive system and breast disorders
Ovarian cyst ruptured
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Reproductive system and breast disorders
Varicocele
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.43%
1/233 • 52 weeks
|
0.00%
0/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.43%
1/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal pouch
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Surgical and medical procedures
Bladder repair
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/233 • 52 weeks
|
0.44%
1/228 • 52 weeks
|
Other adverse events
| Measure |
Mannitol
n=233 participants at risk
Inhaled mannitol
Inhaled mannitol: 400mg BD for 52 weeks
|
Control
n=228 participants at risk
Matched control: Inhaled mannitol 50mg BD for 52 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
6.4%
15/233 • 52 weeks
|
9.2%
21/228 • 52 weeks
|
|
Gastrointestinal disorders
Nausea
|
6.0%
14/233 • 52 weeks
|
7.9%
18/228 • 52 weeks
|
|
General disorders
Condition aggravated
|
63.9%
149/233 • 52 weeks
|
69.7%
159/228 • 52 weeks
|
|
Infections and infestations
Lower respiratory tract infection
|
6.9%
16/233 • 52 weeks
|
9.2%
21/228 • 52 weeks
|
|
Infections and infestations
Lower respiratory tract infection bacterial
|
5.2%
12/233 • 52 weeks
|
3.9%
9/228 • 52 weeks
|
|
Infections and infestations
Nasopharyngitis
|
15.5%
36/233 • 52 weeks
|
13.2%
30/228 • 52 weeks
|
|
Infections and infestations
Sinusitis
|
7.3%
17/233 • 52 weeks
|
6.1%
14/228 • 52 weeks
|
|
Investigations
Bacteia sputum identified
|
12.9%
30/233 • 52 weeks
|
13.2%
30/228 • 52 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.2%
19/233 • 52 weeks
|
5.7%
13/228 • 52 weeks
|
|
Nervous system disorders
Headache
|
11.6%
27/233 • 52 weeks
|
14.0%
32/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.9%
30/233 • 52 weeks
|
9.6%
22/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dsypnoea
|
8.6%
20/233 • 52 weeks
|
7.0%
16/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
10.3%
24/233 • 52 weeks
|
10.1%
23/228 • 52 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
4.3%
10/233 • 52 weeks
|
7.9%
18/228 • 52 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60