Long Term Administration of Inhaled Mannitol in Cystic Fibrosis

• ClinicalTrials.gov Identifier: NCT00630812
• Recruitment Status: Completed
• First Posted: March 7, 2008
• Results First Posted: October 9, 2020
• Last Update Posted: October 9, 2020
• Sponsor: Pharmaxis
• Collaborators: ethica Clinical Research Inc.; Europe: KasaConsult bvba, Hoegaarden, Belgium; Argentina: Resolution Latin America; Buenos Aires, Argentina
• Information provided by (Responsible Party): Pharmaxis

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cystic Fibrosis
• Interventions: Drug: inhaled mannitol; Drug: Placebo comparator
• Enrollment: 318

Participant Flow

Recruitment Details
Pre-assignment Details	Patients underwent a mannitol tolerance test (MTT) to gauge tolerance to a test dose of mannitol. 318 patients were then randomised - only 305 of the randomised patients went on to receive a dose of study medication. Patients who did not start medication (13) were not included in the modified ITT population (mITT)

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description	active treatment inhaled mannitol: 400 mg twice a day (BD) for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Period Title: Randomisation to First Dose
Started	192	126
Completed	184	121
Not Completed	8	5
Reason Not Completed
Adverse Event	1	1
Withdrawal by Subject	2	3
Lost to Follow-up	1	0
Protocol Violation	4	1
Period Title: Double Blind Treatment Period
Started [1]	184	121
Completed	153	107
Not Completed	31	14
Reason Not Completed
Adverse Event	13	5
Lost to Follow-up	1	0
Physician Decision	2	1
Protocol Violation	1	0
Withdrawal by Subject	13	7
Wanted to take drug in non-protocol way	1	0
Non-compliance	0	1
[1] Randomised and received first dose (mITT population). Patients not starting treatment are excluded

Baseline Characteristics

Arm/Group Title		Mannitol 400mg	Control	Total
Arm/Group Description		active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase	Total of all reporting groups
Overall Number of Baseline Participants		184	121	305
Baseline Analysis Population Description		Randomised and Treated (mITT)
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	184 participants	121 participants	305 participants
	<=18 years	91 49.5%	63 52.1%	154 50.5%
	Between 18 and 65 years	93 50.5%	58 47.9%	151 49.5%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	184 participants	121 participants	305 participants
	Female	90 48.9%	58 47.9%	148 48.5%
	Male	94 51.1%	63 52.1%	157 51.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	184 participants	121 participants	305 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 1.1%	2 1.7%	4 1.3%
	White	182 98.9%	119 98.3%	301 98.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	184 participants	121 participants	305 participants
Canada		11	9	20
Argentina		48	32	80
Netherlands		2	2	4
Belgium		10	6	16
United States		85	54	139
France		14	9	23
Germany		14	9	23
Hospitalisations in year prior to study participation; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	184 participants	121 participants	305 participants
	0 hospitalisations	114 62.0%	76 62.8%	190 62.3%
	1 hospitalisation	41 22.3%	30 24.8%	71 23.3%
	2 hospitalisations	21 11.4%	9 7.4%	30 9.8%
	3 hospitalisations	4 2.2%	4 3.3%	8 2.6%
	>3 hospitalisations	4 2.2%	2 1.7%	6 2.0%
Pulmonary exacerbations in year prior to study participation; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	184 participants	121 participants	305 participants
	0 exacerbations	104 56.5%	74 61.2%	178 58.4%
	1 exacerbation	45 24.5%	28 23.1%	73 23.9%
	2 exacerbations	26 14.1%	14 11.6%	40 13.1%
	3 exacerbations	4 2.2%	3 2.5%	7 2.3%
	>3 exacerbations	5 2.7%	2 1.7%	7 2.3%
CF mutation [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	184 participants	121 participants	305 participants
	Both deltaF508	77 41.8%	45 37.2%	122 40.0%
	One deltaF508	57 31.0%	52 43.0%	109 35.7%
	At least one other known mutation	15 8.2%	5 4.1%	20 6.6%
	Both unknown	35 19.0%	19 15.7%	54 17.7%
		[1] Measure Description: Cystic Fibrosis (CF) mutation

Outcome Measures

1. Primary Outcome

Title	Change in Absolute FEV1 From Baseline Over 26 Weeks
Description	Change from baseline in forced expiratory volume at one second (FEV1) averaged over 26 weeks (measured at 6,14 and 26 weeks) The mean absolute change from baseline FEV1 (mL) over 26 weeks (measured at week 6, 14 and 26) will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach.Least square means presented are for the average change over the 6, 14, and 26 week visits.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

mITT (modified intent to treat) - patients randomised and treated with at least one dose of study medication)

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	184	121
Least Squares Mean (95% Confidence Interval); Unit of Measure: mL
	106.53; (62.43 to 150.62)	52.38; (2.09 to 102.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.059
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	54.14
	Confidence Interval	(2-Sided) 95%; -1.97 to 110.26
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.041
	Comments	Response defined as change of >=100mL at week 26
	Method	Regression, Logistic
	Comments	45.7% response on Mannitol 400mg, 35.5% on Control
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.69
	Confidence Interval	(2-Sided) 95%; 1.02 to 2.80
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change in FEV1 From Baseline Over 26 Weeks - Dornase Users
Description	In the subset of dornase users, the mean absolute change from baseline FEV1 (mL) averaged over 26 weeks (measured at week 6, 14 and 26) will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach. Least square means presented are for the average change over the 6, 14, and 26 week visits. Change from baseline over 26 weeks (measured at 6,14, 26 weeks) in subset of dornase users
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

Note these are subset of dornase users - effect in dornase users was estimated using a model fitted using data from all patients

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	137	92
Least Squares Mean (95% Confidence Interval); Unit of Measure: mL
	78.60; (27.64 to 129.56)	35.11; (-20.99 to 91.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.177
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	43.49
	Confidence Interval	(2-Sided) 95%; -19.8 to 106.78
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Rate of Protocol Defined Pulmonary Exacerbations (PDPE)
Description	Exacerbations treated with IV antibiotics and with at least 4 signs and symptoms according to Fuchs criteria (1994). Summary table presents the number with 0, 1,2 and 3 PDPEs during the 26 week treatment period.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

mITT (randomised and treated)

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	184	121
Measure Type: Count of Participants; Unit of Measure: Participants
With 1 PDPE	21 11.4%	18 14.9%
With 2 PDPE	6 3.3%	4 3.3%
With 3 PDPE	1 0.5%	1 0.8%
No PDPEs	156 84.8%	98 81.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.520
	Comments	[Not Specified]
	Method	Poisson regression
	Comments	Offset of the natural logarithm of follow-up time
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.41
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Hospitalisations Associated With Protocol Defined Pulmonary Exacerbations (PDPEs)
Description	The number of hospitalisations is summarised and then the rate per person is analysed.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	184	121
Measure Type: Count of Participants; Unit of Measure: Participants
0 hospitalisations	162 88.0%	102 84.3%
1 hospitalisation	18 9.8%	14 11.6%
2 hospitalisations	3 1.6%	5 4.1%
3 hospitalisations	1 0.5%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.328
	Comments	[Not Specified]
	Method	Poisson regression
	Comments	Offset of the natural logarithm of follow-up time
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.42 to 1.33
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Antibiotic Use Associated With PDPEs
Description	Number of courses per person in the 26 week period is summarised and then the rate per person analysed.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	184	121
Measure Type: Count of Participants; Unit of Measure: Participants
0 courses	156 84.8%	98 81.0%
1 course	22 12.0%	19 15.7%
2 courses	5 2.7%	2 1.7%
3 courses	1 0.5%	2 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.368
	Comments	[Not Specified]
	Method	Poisson regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.15
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Absolute Change in FEV1 Percent Predicted at 26 Weeks
Description	Change from baseline at 26 weeks in FEV1 percent predicted with BOCF for those with missing values at week 26
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

Baseline Observation carried forward (BOCF) implemented for those with missing values at visit 4

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	184	121
Least Squares Mean (95% Confidence Interval); Unit of Measure: % of predicted
	3.14; (1.49 to 4.78)	0.72; (-1.18 to 2.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.024
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.42
	Confidence Interval	(2-Sided) 95%; 0.33 to 4.51
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change in FVC (mL) Across 26 Weeks
Description	Change from baseline in forced vital capacity (FVC) across 26 weeks (measured at 6,14 and 26 weeks)
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	184	121
Least Squares Mean (95% Confidence Interval); Unit of Measure: mL
	136.33; (88.54 to 184.11)	64.98; (10.58 to 119.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.022
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	71.35
	Confidence Interval	(2-Sided) 95%; 10.57 to 132.13
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Change From Baseline FEF25-75 (mL/s) Over 26 Weeks
Description	Change from baseline in forced expiratory flow at 25-75% of forced vital capacity (FEF25-75) (mL/s) averaged over 26 weeks (measured at 6,14 and 26 weeks) The mean absolute change from baseline over 26 weeks (measured at week 6, 14 and 26) was compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach. Least square means presented are for the average change over the 6, 14, and 26 week visits.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	184	121
Least Squares Mean (95% Confidence Interval); Unit of Measure: mL/s
	84.65; (6.66 to 162.63)	50.31; (-38.24 to 138.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.49
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	34.34
	Confidence Interval	(2-Sided) 95%; -63.47 to 132.14
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Sputum Weight at Baseline in Response to First Dose of Treatment
Description	Sputum was collected during and for 30 minutes following the administration of the first dose of study treatment.
Time Frame	up to 30 mins after first dose of trial treatment

Outcome Measure Data

Analysis Population Description

Patients randomised and treated who have sputum weight results available.

Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description:	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Overall Number of Participants Analyzed	180	114
Mean (Standard Deviation); Unit of Measure: g
	4.9 (6.18)	3.5 (4.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mannitol 400mg, Control
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.042
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Adverse Events

Time Frame	26 weeks
Adverse Event Reporting Description	Safety information reported is for the 26 week double blind period only
Arm/Group Title	Mannitol 400mg	Control
Arm/Group Description	active treatment inhaled mannitol: 400 mg BD for 26 + 26 weeks	Control (40mg inhaled mannitol) : BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
All-Cause Mortality
	Mannitol 400mg	Control
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/184 (0.00%)	1/121 (0.83%)
Serious Adverse Events
	Mannitol 400mg	Control
	Affected / at Risk (%)	Affected / at Risk (%)
Total	31/184 (16.85%)	30/121 (24.79%)
Gastrointestinal disorders
Pancreatitis * 1	1/184 (0.54%)	0/121 (0.00%)
Distal intestinal obstruction syndrome * 1	0/184 (0.00%)	1/121 (0.83%)
Intestinal obstruction * 1	0/184 (0.00%)	1/121 (0.83%)
Pancreatis acute * 1	0/184 (0.00%)	1/121 (0.83%)
Vomiting * 1	0/184 (0.00%)	1/121 (0.83%)
General disorders
Condition Aggravated * 1 [1]	27/184 (14.67%)	20/121 (16.53%)
Hepatobiliary disorders
Cholecystitis * 1	1/184 (0.54%)	0/121 (0.00%)
Infections and infestations
Bronchopneumonia * 1	1/184 (0.54%)	0/121 (0.00%)
Lower respiratory tract infection * 1	0/184 (0.00%)	3/121 (2.48%)
Acute tonsillitis * 1	0/184 (0.00%)	1/121 (0.83%)
Appendicitis * 1	0/184 (0.00%)	1/121 (0.83%)
Pneumonia * 1	0/184 (0.00%)	1/121 (0.83%)
Pneumonia bacterial * 1	0/184 (0.00%)	1/121 (0.83%)
Pyelonephritis * 1	0/184 (0.00%)	1/121 (0.83%)
Metabolism and nutrition disorders
Diabetes mellitus * 1	1/184 (0.54%)	0/121 (0.00%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis * 1	2/184 (1.09%)	0/121 (0.00%)
Asthmatic Crisis * 1	0/184 (0.00%)	1/121 (0.83%)
Pleuritic Pain * 1	0/184 (0.00%)	1/121 (0.83%)
Pneumothorax * 1	0/184 (0.00%)	1/121 (0.83%)
1 Term from vocabulary, MedDRA (11.0); * Indicates events were collected by non-systematic assessment; [1] pulmonary exacerbations were coded to condition aggravated
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Mannitol 400mg	Control
	Affected / at Risk (%)	Affected / at Risk (%)
Total	165/184 (89.67%)	106/121 (87.60%)
Gastrointestinal disorders
Abdominal pain * 1	14/184 (7.61%)	8/121 (6.61%)
Abdominal pain upper * 1	6/184 (3.26%)	7/121 (5.79%)
General disorders
Condition Aggravated * 1 [1]	57/184 (30.98%)	41/121 (33.88%)
Pyrexia * 1	17/184 (9.24%)	13/121 (10.74%)
Infections and infestations
Nasopharyngitis * 1	11/184 (5.98%)	6/121 (4.96%)
Upper respiratory tract infection * 1	10/184 (5.43%)	11/121 (9.09%)
Sinusitis * 1	8/184 (4.35%)	7/121 (5.79%)
Nervous system disorders
Headache * 1	26/184 (14.13%)	22/121 (18.18%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	28/184 (15.22%)	16/121 (13.22%)
Pharyngolaryngeal pain * 1	19/184 (10.33%)	13/121 (10.74%)
Haemoptysis * 1	11/184 (5.98%)	3/121 (2.48%)
1 Term from vocabulary, MedDRA (11.0); * Indicates events were collected by non-systematic assessment; [1] Pulmonary Exacerbations were coded to condition aggravated

Limitations and 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.

Results Point of Contact

• Name/Title: Brett Charlton
• Organization: Pharmaxis
• Phone: 02 94547210
• EMail: Brett.Charlton@pharmaxis.com.au

Publications:

Daviskas E, Anderson SD. Hyperosmolar agents and clearance of mucus in the diseased airway. J Aerosol Med. 2006 Spring;19(1):100-9. Review.

Daviskas E, Anderson SD, Gomes K, Briffa P, Cochrane B, Chan HK, Young IH, Rubin BK. Inhaled mannitol for the treatment of mucociliary dysfunction in patients with bronchiectasis: effect on lung function, health status and sputum. Respirology. 2005 Jan;10(1):46-56.

Daviskas E, Robinson M, Anderson SD, Bye PT. Osmotic stimuli increase clearance of mucus in patients with mucociliary dysfunction. J Aerosol Med. 2002 Fall;15(3):331-41. Review.

Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol. 2002 Apr;33(4):293-306. Review.

Daviskas E, Anderson SD, Eberl S, Chan HK, Young IH. The 24-h effect of mannitol on the clearance of mucus in patients with bronchiectasis. Chest. 2001 Feb;119(2):414-21.

Robinson M, Daviskas E, Eberl S, Baker J, Chan HK, Anderson SD, Bye PT. The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study. Eur Respir J. 1999 Sep;14(3):678-85.

Daviskas E, Anderson SD, Eberl S, Chan HK, Bautovich G. Inhalation of dry powder mannitol improves clearance of mucus in patients with bronchiectasis. Am J Respir Crit Care Med. 1999 Jun;159(6):1843-8.

Daviskas E, Anderson SD, Brannan JD, Chan HK, Eberl S, Bautovich G. Inhalation of dry-powder mannitol increases mucociliary clearance. Eur Respir J. 1997 Nov;10(11):2449-54.

Jaques A, Daviskas E, Turton JA, McKay K, Cooper P, Stirling RG, Robertson CF, Bye PTP, LeSouëf PN, Shadbolt B, Anderson SD, Charlton B. Inhaled mannitol improves lung function in cystic fibrosis. Chest. 2008 Jun;133(6):1388-1396. doi: 10.1378/chest.07-2294. Epub 2008 Mar 13.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nevitt SJ, Thornton J, Murray CS, Dwyer T. Inhaled mannitol for cystic fibrosis. Cochrane Database Syst Rev. 2020 May 1;5:CD008649. doi: 10.1002/14651858.CD008649.pub4.

Aitken ML, Bellon G, De Boeck K, Flume PA, Fox HG, Geller DE, Haarman EG, Hebestreit HU, Lapey A, Schou IM, Zuckerman JB, Charlton B; CF302 Investigators. Long-term inhaled dry powder mannitol in cystic fibrosis: an international randomized study. Am J Respir Crit Care Med. 2012 Mar 15;185(6):645-52. doi: 10.1164/rccm.201109-1666OC. Epub 2011 Dec 28.

• Responsible Party: Pharmaxis
• ClinicalTrials.gov Identifier: NCT00630812
• Other Study ID Numbers: DPM-CF-302
• First Submitted: February 27, 2008
• First Posted: March 7, 2008
• Results First Submitted: August 11, 2020
• Results First Posted: October 9, 2020
• Last Update Posted: October 9, 2020