Long Term Administration of Inhaled Mannitol in Cystic Fibrosis

Phase 3

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: Placebo comparator; Drug: inhaled mannitol

• Registration Number: NCT00630812
• Lead Sponsor: Syntara

Brief Summary

The purpose of this study is to examine the efficacy and safety of 26 weeks treatment with inhaled mannitol in subjects with cystic fibrosis. Previous studies have demonstrated improvements in lung function, mucociliary clearance, changes in physical properties of mucus, 24 hour sputum weight and quality of life. The results of this study are to further investigate and confirm these findings in addition to examine the effect on antibiotic use and chest infections. It is hypothesised that inhaled mannitol will have beneficial effects compared to a control treatment. An open label phase of 26 weeks duration will follow the blinded 26 week phase. During the open label phase all subjects will receive active treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-02-27
• Study First Submitted QC: 2008-02-27
• Study First Posted: 2008-03-07
• Study Start: 2008-09
• Primary Completion: 2010-04
• Study Completion: 2010-11
• Disposition First Submitted: 2012-08-06
• Disposition First Submitted QC: 2012-08-06
• Disposition First Posted: 2012-08-15
• Results First Submitted: 2020-08-11
• Status Verified: 2020-10
• Results First Submitted QC: 2020-10-06
• Last Update Submitted: 2020-10-06
• Results First Posted: 2020-10-09
• Last Update Posted: 2020-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 318

Inclusion Criteria

1. Have given written informed consent to participate in this study in accordance with local regulations
2. Have a confirmed diagnosis of cystic fibrosis (positive sweat chloride value ≥ 60 mEq/L) and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype)
3. Be aged > 6 years old
4. Have FEV1 >40 % and < 90% predicted
5. Be able to perform all the techniques necessary to measure lung function

Exclusion Criteria

1. Investigators, site personnel directly affiliated with this study, or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted.

2. Be considered "terminally ill" or eligible for lung transplantation

3. Have had a lung transplant

4. Be using nebulized hypertonic saline in the 4 weeks prior to visit 1

5. Have had a significant episode of hemoptysis (>60 mL) in the three months prior to enrolment

6. Have had a myocardial infarction in the three months prior to enrolment

7. Have had a cerebral vascular accident in the three months prior to enrolment

8. Have had major ocular surgery in the three months prior to enrolment

9. Have had major abdominal, chest or brain surgery in the three months prior to enrolment

10. Have a known cerebral, aortic or abdominal aneurysm

11. Be breast feeding or pregnant, or plan to become pregnant while in the study

12. Be using an unreliable form of contraception (female subjects at risk of pregnancy only)

13. Be participating in another investigative drug study, parallel to, or within 4 weeks of visit 0

14. Have a known allergy to mannitol

15. Be using beta blockers

16. Have uncontrolled hypertension - systolic BP > 190 and / or diastolic BP > 100

17. Have a condition or be in a situation which in the Investigator's opinion may put the subject at significant risk, may confound results or may interfere significantly with the patient's participation in the study

18. Be 'Mannitol Tolerance Test positive'

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	Placebo comparator	-
A	inhaled mannitol	active treatment

Primary Outcome Measures

Name	Time	Method
Change in Absolute FEV1 From Baseline Over 26 Weeks	26 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline FEF25-75 (mL/s) Over 26 Weeks	26 weeks	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.
Change in FEV1 From Baseline Over 26 Weeks - Dornase Users	26 weeks	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
Rate of Protocol Defined Pulmonary Exacerbations (PDPE)	26 weeks	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.
Hospitalisations Associated With Protocol Defined Pulmonary Exacerbations (PDPEs)	26 weeks	The number of hospitalisations is summarised and then the rate per person is analysed.
Absolute Change in FEV1 Percent Predicted at 26 Weeks	26 weeks	Change from baseline at 26 weeks in FEV1 percent predicted with BOCF for those with missing values at week 26
Antibiotic Use Associated With PDPEs	26 weeks	Number of courses per person in the 26 week period is summarised and then the rate per person analysed.
Change in FVC (mL) Across 26 Weeks	26 weeks	Change from baseline in forced vital capacity (FVC) across 26 weeks (measured at 6,14 and 26 weeks)
Sputum Weight at Baseline in Response to First Dose of Treatment	up to 30 mins after first dose of trial treatment	Sputum was collected during and for 30 minutes following the administration of the first dose of study treatment.

Trial Locations

Locations (53)

University of Arizona; 🇺🇸 Tucson, Arizona, United States

Central Connecticut Cystic Fibrosis Center; 🇺🇸 Hartford, Connecticut, United States

Nemours Childrens Clinic; 🇺🇸 Jacksonville, Florida, United States

Batchelor Children's Research Institute - University of Miami; 🇺🇸 Miami, Florida, United States

Nemours Children's Clinic Orlando; 🇺🇸 Orlando, Florida, United States

St Lukes CF Center of Idaho; 🇺🇸 Idaho, Idaho, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Louisiana State University Health Sciences Center; 🇺🇸 Shreveport, Louisiana, United States

Maine Pediatric Specialty Group; 🇺🇸 Portland, Maine, United States

John Hopkins; 🇺🇸 Baltimore, Maryland, United States

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