Long Term Administration of Inhaled Mannitol in Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: inhaled mannitol; Placebo comparator
Intervention description: 400 mg BD for 26 + 26 weeks; BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase
Intervention MeSH terms: Mannitol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 318.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: cystic fibrosis; mannitol; mucoactive

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.
    

Eligibility criteria:

        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'

             -