Long Term Administration of Inhaled Mannitol in Cystic Fibrosis
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: Placebo comparator
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 318
- Have given written informed consent to participate in this study in accordance with local regulations
- 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)
- Be aged > 6 years old
- Have FEV1 >40 % and < 90% predicted
- Be able to perform all the techniques necessary to measure lung function
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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.
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Be considered "terminally ill" or eligible for lung transplantation
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Have had a lung transplant
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Be using nebulized hypertonic saline in the 4 weeks prior to visit 1
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Have had a significant episode of hemoptysis (>60 mL) in the three months prior to enrolment
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Have had a myocardial infarction in the three months prior to enrolment
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Have had a cerebral vascular accident in the three months prior to enrolment
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Have had major ocular surgery in the three months prior to enrolment
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Have had major abdominal, chest or brain surgery in the three months prior to enrolment
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Have a known cerebral, aortic or abdominal aneurysm
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Be breast feeding or pregnant, or plan to become pregnant while in the study
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Be using an unreliable form of contraception (female subjects at risk of pregnancy only)
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Be participating in another investigative drug study, parallel to, or within 4 weeks of visit 0
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Have a known allergy to mannitol
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Be using beta blockers
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Have uncontrolled hypertension - systolic BP > 190 and / or diastolic BP > 100
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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
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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 usersRate 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)
John Hopkins
🇺🇸Baltimore, Maryland, United States
University of Missouri
🇺🇸Columbia, Missouri, United States
University of Washington medical centre
🇺🇸Seattle, Washington, United States
Nemours Childrens Clinic
🇺🇸Jacksonville, Florida, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Maine Pediatric Specialty Group
🇺🇸Portland, Maine, United States
Women and Childrens Hospital of Buffalo
🇺🇸Buffalo, New York, United States
The Toledo Hospital and Toledo Childrens Hospital
🇺🇸Toledo, Ohio, United States
St Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Atención Integral en Reumatologia (AIR)
🇦🇷Buenos Aires, Argentina
UZ Brussel Laarbeeklan 101
🇧🇪Brussel, Belgium
The Children's Asthma Clinic
🇨🇦London, Ontario, Canada
UZ Gasthuisberg
🇧🇪Leuven, Belgium
Foothills medical center
🇨🇦Calgary, Alberta, Canada
Hopital Andre Mignot
🇫🇷Le Chesnay, Cedix, France
Hopital Mere-Enfant
🇫🇷Nantes, Cedex, France
QEII Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
Hopital Jeanne de Flandre
🇫🇷Lille CEDEX, Lille, France
Hopital Femme-Mere-Enfents
🇫🇷Bron Cedex, Lyon, France
Hopital de Hautepierre
🇫🇷Strasbourg CEDEX, Strasbourg, France
Hopital Robert Debre
🇫🇷Paris, France
University of Munich Medizinischen Klinik Innenstadt
🇩🇪Munchen, Germany
Universitats Kinderklinik Tubungen Wurzburg
🇩🇪Tubingen, Germany
Universitats Kinderklinik Wurzburg
🇩🇪Wurzburg, Germany
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Sanford Children's Specialty Clinic
🇺🇸Sioux Falls, South Dakota, United States
Central Connecticut Cystic Fibrosis Center
🇺🇸Hartford, Connecticut, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
St Lukes CF Center of Idaho
🇺🇸Idaho, Idaho, United States
Hospital Interzonal Dr Jose Penna Bahia Blanca
🇦🇷Bahia Blanca, Buenos Aires, Argentina
Hospital Gral. de Ninos Pedro de Elizalde
🇦🇷Ciudad Autonoma, Buenos Aires, Argentina
Le Bonheur Children's Medical Center
🇺🇸Memphis, Tennessee, United States
Hospital de Ninos Superiora Sor Maria Ludovica de La Plata
🇦🇷La Plata, Buenos Aires, Argentina
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Clinica Universitaria Privada Reina Fabiola - Universidad Cotolica de Cordoba
🇦🇷Cordoba, Argentina
Louisiana State University Health Sciences Center
🇺🇸Shreveport, Louisiana, United States
Pediatrics Respiratory Medicine
🇧🇪Edegem, Antwerpen, Belgium
Hopital Universitaire Reine Fabiola
🇧🇪Bruxelles, Brussel, Belgium
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Hospital de Ninos del la Santisima Trinidad
🇦🇷Cordoba, Argentina
Academic Medical Centre
🇳🇱Amsterdam, Netherlands
Hospital de Ninos Dr Ricardo Gutierrez, Pediatria
🇦🇷Caba, Buenos Aires, Argentina
Hospital Pediatrico Dr Humberto J Notti
🇦🇷Guaymallen, Mendosa, Argentina
Batchelor Children's Research Institute - University of Miami
🇺🇸Miami, Florida, United States
Nemours Children's Clinic Orlando
🇺🇸Orlando, Florida, United States
Medical University of SC
🇺🇸Charleston, South Carolina, United States
Alamo Clinical Research Associates
🇺🇸San Antonio, Texas, United States
Christus Santa Rosa Children's Hospital Cystic Fibrosis Center
🇺🇸San Antonio, Texas, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Pediatric Research, VCU Medical Centre
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Nebraska Medical Center - Nebraska Regional CF Center
🇺🇸Omaha, Nebraska, United States
Children's Chest Associates of Austin
🇺🇸Austin, Texas, United States