Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis
- Registration Number
- NCT00669331
- Lead Sponsor
- Syntara
- Brief Summary
No gold standard therapy exists for clearing mucus from the airways of patients with bronchiectasis. While rhDNase has a proven place in the treatment of cystic fibrosis (CF), it failed to improve Forced expiratory volume in one second (FEV1) in a short-term non-CF bronchiectasis study and has been shown to be detrimental after 6 months therapy in non CF bronchiectasis, moreover it has no proven effect on mucociliary clearance. Hypertonic saline has been shown to have a comparable mode of action to inhaled mannitol, but has yet to be examined as a long term treatment option in bronchiectasis.
The purpose of this study is to examine the efficacy and safety of 52 weeks treatment with inhaled mannitol in subjects with non-cystic fibrosis bronchiectasis. Previous studies with inhaled mannitol have demonstrated improvement in mucociliary clearance; mucus rehydration; improvement in quality of life and respiratory symptoms in patients with bronchiectasis and pulmonary function in cystic fibrosis. The results of this current study in combination with a recently completed 3 month study seek to confirm these early findings and to extend the evidence to support its use as a mucoactive therapy in subjects with bronchiectasis.
We hypothesize that mannitol will improve the overall health and hygiene of the lung through regular and effective clearing of the mucus load. As a consequence of the reduction in mucus load and inflammatory process, the frequency of bronchiectasis related pulmonary exacerbations and the need for exacerbation related antibiotic treatment should fall. Days in hospital and community health care costs are expected to change in line with improvements in respiratory health.
Finally, we plan to demonstrate that inhaled mannitol is safe and well tolerated over a 52 week period. We will test these hypotheses using 400 mg mannitol twice daily (BD) against control.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 485
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Matched control Matched control - inhaled mannitol 50mg Mannitol Inhaled mannitol Inhaled mannitol 400mg
- Primary Outcome Measures
Name Time Method Rate of Graded Pulmonary Exacerbations 52 weeks A graded pulmonary exacerbation was defined as a worsening in signs and symptoms requiring a change in treatment (Center for Drug Evaluation and Research (CDER), 2007). Grade I was required 3 main signs and symptoms, Grade II 2 main signs and symptoms and Grade III 1 main and one or more minor signs and symptoms. Main signs and symptoms were increased cough, sputum volume or sputum purulence. Minor were upper respiratory tract infection, fever, increased wheezing, increased dyspnea, increase in respiratory rate, increase in cardiac frequency of \>20%, and increased malaise, fatigue or lethargy. Rate is defined as the number of all GPE events observed in one treatment year
- Secondary Outcome Measures
Name Time Method Safety Profile - Hematology 52 weeks hematology assessed as clinically significant abnormal FBC (Full Blood count) at any point post baseline.
• (Exploratory) Number of Hospitalizations Due to Pulmonary Exacerbations 52 weeks Mean rate of hospitalisations (number/year) summarised and analysed to take account of differing follow-up times.
Quality of Life as Measured by the St. Georges Respiratory Questionnaire (SGRQ) Total Score 52 weeks The SGRQ was collected at baseline, week 6, week 16, week 28, week 40 and week 52. Change in total score was calculated from baseline. Total scores are a weighted sum across all questions. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. Higher scores indicate lower quality of life. Outcome data table gives the raw mean total score at each visit.
Antibiotic Use Prescribed for Treated Pulmonary Exacerbations 52 weeks Rate of antibiotic treated graded pulmonary exacerbations, using the same definition of a graded pulmonary exacerbation as the primary endpoint. A graded pulmonary exacerbation was considered to be anti-biotic treated if use of oral, IV or inhaled antibiotic use was recorded related to the GPE event.
Time to First Graded Exacerbation 52 weeks Time to first graded exacerbation is defined as the duration (in months) from the randomisation date to the start of the first reported graded PE during the on-treatment period. Patients without reported graded PE event will be censored at the last participation.
Duration of Graded Exacerbations 52 weeks Duration of graded exacerbations is defined as the number of days with graded PE within one treatment year. Mean days estimated via negative binomial model with treatment, region and baseline pulmonary exacerbation rate as predictors, with log of follow-up time as the offset variable
Sputum Volume 52 weeks 24 hour sputum weight, measured at baseline, week 6, week 16, week 28, week 40, week 52
Daytime Sleepiness Scores 52 weeks Epworth Sleepiness Scale (ESS) score was calculated as the sum of scores for each of eight individual questions, such that a total score of zero represents no daytime sleepiness, and a total score of 24 represents the maximum degree of daytime sleepiness. Measured at baseline, 6 weeks, 16 weeks, 28 weeks, 40 weeks, 52 weeks
Lung Function - Change in FEV1 (Forced Expiratory Volume in One Second) 52 weeks Lung Function - Change in FVC (Forced Vital Capacity) 52 weeks Lung Function - Change in FEV1/FVC 52 weeks FEV1 expressed as a ratio of FVC. Endpoint is expressed as a percentage ie FEV1/FVC\*100
Lung Function - Change in FEF25-75 (Forced Expiratory Flow Rate Averaged Over 25th -75th Percentile of FVC) 52 weeks Safety Profile - Sputum Microbiology 52 weeks sputum microbiology assessed as the presence of abnormal flora in sputum sample taken at any post baseline visit
Safety Profile - Clinical Chemistry 52 weeks Clinical chemistry was assessed as clinically significant abnormal liver function test and clinically significant abnormal urea/electrolyte test at any point post baseline.
Trial Locations
- Locations (83)
University of Miami
🇺🇸Miami, Florida, United States
Florida Pulmonary Research
🇺🇸Winter Park, Florida, United States
The University of Chicago Hospitals
🇺🇸Chicago, Illinois, United States
Chest Medicine Clinical Services, LLC
🇺🇸Skokie, Illinois, United States
Saint Luke's Hospital
🇺🇸Chesterfield, Missouri, United States
St Vincent's Hospital
🇦🇺Fitzroy, Victoria, Australia
Hospital Zonal Especializado en Agudos y Cronicos "Dr Antonio A. Cetrangolo
🇦🇷Florida Partido de Vicente López, Provincia de Buenos Aires, Argentina
Clinica del Torax
🇦🇷Rosario, Provincia de Santa Fe, Argentina
Universidad de Chile
🇨🇱Santiago de Chile, Santiago, Chile
Green Lane Clinical Centre
🇳🇿Greenlane, Auckland, New Zealand
Medisch Centrum Leeuwarden (MCL) - Department of Pulmonology
🇳🇱Leeuwarden, Leeuwarden AD, Netherlands
Royal Derby Hospital
🇬🇧Derby, Derbyshire, United Kingdom
Middlemore Hospital
🇳🇿Auckland, New Zealand
Sheffield Northern General Hospital
🇬🇧Sheffield, South Yorkshire, United Kingdom
Ashford & St Peters Hospital
🇬🇧Chertsey, Surrey, United Kingdom
Llandough Hospital
🇬🇧Cardiff, Vale of Glamorgan, United Kingdom
Birmingam Queen Elizabeth Hospital
🇬🇧Birmingham, West Midlands, United Kingdom
Freeman Hospital
🇬🇧Newcastle-upon-Tyne, United Kingdom
North Tyneside General Hospital
🇬🇧North Shields, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Wrexham Maelor Hospital
🇬🇧Wrexham, United Kingdom
Corporacion medica de General San Martin
🇦🇷Mathew 4071, San Martin Provincia de Buenos Aires, Argentina
Hospital Privado - Centro Medico de Cordoba
🇦🇷Cordoba, Provincia de Cordoba, Argentina
UZ Leuven (University Hospital Leuven) - Depatment of Pulmonary Medicine
🇧🇪Leuven, Belgium
Churchill Hospital
🇬🇧Headington, Oxfordshire, United Kingdom
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Insares
🇦🇷Mendoza, Provincia de Mendoza, Argentina
Investigaciones en Patologias Respiratorias
🇦🇷San Miguel de Tucumán, Provincia de Tucumán, Argentina
Atrium MC -Department of Pulmonary Diseases
🇳🇱Heerlen, Netherlands
Instituto Cardiovascular de Rosario
🇦🇷Rosario, Provincia de Santa Fe, Argentina
Hospital Interzonal General de Agudos "Dr Jose Penna"
🇦🇷Bahia Bianca, Provinica de Buenos Aires, Argentina
Centro Médico Dra. De Salvo
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Stafford Hospital
🇬🇧Stafford, Staffordshire, United Kingdom
Glenfield Hospital
🇬🇧Leicester, Leicestershire, United Kingdom
The Rooms of Dr C Steinfort
🇦🇺Geelong, Victoria, Australia
West Wales General Hospital
🇬🇧Carmarthen, Carmarthenshire, United Kingdom
National Jewish Medical and Research Center
🇺🇸Denver, Colorado, United States
The Oregon Clinic, PC/Pulmonary Division
🇺🇸Portland, Oregon, United States
Alamo Clinical Research Associates
🇺🇸San Antonio, Texas, United States
Medizinische Hochschule Hannover Klinik für Pneumologie
🇩🇪Hannover, Niedersachsen, Germany
Pneumologisch Studienzentrum
🇩🇪Leipzig, Sachsen, Germany
Torbay Hospital
🇬🇧Torquay, Devon, United Kingdom
University Hospital of North Tees
🇬🇧Stockton, Teeside, United Kingdom
Royal Shrewsbury Hospital
🇬🇧Shrewsbury, Shropshire, United Kingdom
Belfast City Hospital
🇬🇧Belfast, United Kingdom
Wolverhampton New Cross Hospital
🇬🇧Wolverhampton, West Midlands, United Kingdom
University Hospital Aintree
🇬🇧Liverpool, United Kingdom
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of Connecticut Health Center, Pulmonary Division
🇺🇸Farmington, Connecticut, United States
Pulmonary and Allergy Associates
🇺🇸Summit, New Jersey, United States
Research Associates of New York
🇺🇸New York, New York, United States
Centro Privado de Medicina Respiratoria
🇦🇷Entre Rios, Paraná Entre Ríos, Argentina
Allergy and Critical Care Medicine Pulmonary Clinical Research Unit
🇺🇸Rochester, Minnesota, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
University of Pennsylvania Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
South Carolina Pharmaceutical Research
🇺🇸Spartanburg, South Carolina, United States
Centro Respiratorio Quilmes
🇦🇷Quilmes, Provincia de Buenos Aires, Argentina
Instituto Argentino de Investigación Neurológica
🇦🇷Ciudad Autónoma de Buenos Aires, Ciudad Autónoma de Buenos Aires,, Argentina
Sanatorio Parque
🇦🇷Rosario, Provincia de Santa Fe, Argentina
Atención Integral en Reumatología (AIR)
🇦🇷Buenos Aires, Argentina
Woolcock Institute of Medical Research
🇦🇺Glebe, New South Wales, Australia
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Repatriation General Hospital
🇦🇺Daws Park, South Australia, Australia
Western Hospital
🇦🇺Footscray, Victoria, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville, South Australia, Australia
ULB Hopital Erasme - Department of Pneumology
🇧🇪Brussels, Belgium
IKF Pneumologie GmbH and Co KG
🇩🇪Frankfurt, Hessen, Germany
Aberdeen Royal Infirmary
🇬🇧Aberdeen, United Kingdom
Waikato Hospital
🇳🇿Hamilton, New Zealand
Cliniques Universitaires St. Luc (UCL) - Department of Pulmonology
🇧🇪Brussels, Belgium
Medisch Centrum Alkmaar - Department of Pulmonary Medicine
🇳🇱Alkmaar, Alkmaar AM, Netherlands
Royal Devon and Exeter Hospital
🇬🇧Exeter, Devon, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Pontificia Universidad Catolica de Chile
🇨🇱Santiago de Chile, Santiago, Chile
Lungen und Bronchialheikunde
🇩🇪Bonn, Nordrhein-Westfalen, Germany
Hospital Regional de Talca
🇨🇱Talca, Chile
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Pulmonary Associates of Richmond, Inc
🇺🇸Richmond, Virginia, United States
Royal Brompton Hospital
🇬🇧London, United Kingdom
Castle Hill Hospital
🇬🇧Cottingham, East Yorkshire, United Kingdom