Long Term Administration of Inhaled Mannitol in Cystic Fibrosis

Syntara318 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

318

Conditions

Cystic Fibrosis

Interventions

Eligibility

Sex: ALLMin age: 6 Years

Medical Language ↔ Plain English

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' \-

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

Outcomes

Primary Outcomes

Change in Absolute FEV1 From Baseline Over 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.

Time frame: 26 weeks

Secondary Outcomes

Change in FEV1 From Baseline Over 26 Weeks - Dornase Users

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

Rate of Protocol Defined Pulmonary Exacerbations (PDPE)

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

Hospitalisations Associated With Protocol Defined Pulmonary Exacerbations (PDPEs)

The number of hospitalisations is summarised and then the rate per person is analysed.

Time frame: 26 weeks

Antibiotic Use Associated With PDPEs

Number of courses per person in the 26 week period is summarised and then the rate per person analysed.

Time frame: 26 weeks

Absolute Change in FEV1 Percent Predicted at 26 Weeks

Change from baseline at 26 weeks in FEV1 percent predicted with BOCF for those with missing values at week 26

Time frame: 26 weeks

Change in FVC (mL) Across 26 Weeks

Change from baseline in forced vital capacity (FVC) across 26 weeks (measured at 6,14 and 26 weeks)

Time frame: 26 weeks

Change From Baseline FEF25-75 (mL/s) Over 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.

Time frame: 26 weeks

Sputum Weight at Baseline in Response to First Dose of Treatment

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