Inhaled Mannitol as a Mucoactive Therapy for Bronchiectasis

NCT ID: NCT00669331

Last Updated: 2016-04-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

485 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-30

Study Completion Date

2014-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Bronchiectasis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Mannitol

Inhaled mannitol 400mg

Group Type EXPERIMENTAL

Inhaled mannitol

Intervention Type DRUG

400mg dose of Mannitol BD (twice a day) for 52 weeks

Control

Matched control - inhaled mannitol 50mg

Group Type PLACEBO_COMPARATOR

Matched control

Intervention Type DRUG

50mg dose of Mannitol BD (twice a day) for 52 weeks

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Inhaled mannitol

400mg dose of Mannitol BD (twice a day) for 52 weeks

Intervention Type DRUG

Matched control

50mg dose of Mannitol BD (twice a day) for 52 weeks

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Have given written informed consent to participate in this study in accordance with local regulations
2. Have documented evidence of confirmed diagnosis of (non-cystic fibrosis) bronchiectasis by computed tomography (CT), High resolution computed tomography (HRCT) or bronchogram
3. Be aged 18 - 85 years inclusive, male and female
4. Have FEV1 (Forced expiratory volume in one second) ≥ 40% and ≤85% predicted\* and ≥1.0L (\*according to NHANES III predicted tables) measured at Visit 0A (V0A)
5. Clinician documented history of at least 2 pulmonary exacerbations, each requiring antibiotic therapy, in the last 12 months prior to Visit 0A (V0A) and a total of at least 4 in the last 2 years prior to Visit 0A
6. Have a total SGRQ (St George's respiratory questionnaire) score of ≥30 at Visit 0B (V0B)
7. Have a production of ≥10g of sputum at Visit 0B Have reported chronic sputum production of ≥1 tablespoon (15mL) per day on the majority of days in the 3 months prior to Visit 0A
8. Be able to perform all the techniques necessary to measure lung function
9. Have FEV1 ≥40% predicted\* and ≥1.0L (\*according to NHANES III 1999 predicted tables) measured at V0B (Baseline result prior to MTT (Mannitol Tolerance Test) administration)

Exclusion Criteria

1. Be 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. Have bronchiectasis as a consequence of cystic fibrosis or focal endobronchial lesion or otherwise curable causes (e.g. foreign body aspiration)
3. Be considered "terminally ill" or listed for transplantation
4. Be using hypertonic saline in the 14 days prior to commencing Visit 0B or thereafter at any time during the study
5. Have previously used inhaled mannitol (Bronchitol) for more than a day
6. Have had a significant episode of hemoptysis (\>60 mL) in the previous 6 months
7. Have had rescue antibiotics in the 4 weeks prior to V0B (chronic background antibiotic therapy accepted)
8. Have smoked within the last 3 months and must not smoke during their participation in the study
9. Have had a myocardial infarction in the three months prior to Visit 0A
10. Have had a cerebral vascular accident in the three months prior to Visit 0A
11. Have had major ocular surgery in the three months prior to Visit 0A
12. Have had major abdominal, chest or brain surgery in the three months prior to Visit 0A
13. Have a known cerebral, aortic or abdominal aneurysm
14. Have actively treated Mycobacterium tuberculosis
15. Have actively treated or unstable nontuberculous mycobacterial (NTM)infection or be under consideration for NTM treatment in the next 12 months
16. Have unstable Allergic bronchopulmonary aspergillosis (ABPA) requiring steroid therapy (≤5mg dose oral steroids in stable ABPA accepted)
17. Have end stage interstitial lung disease
18. Have active malignancy including melanoma (other skin carcinomas exempted). Remissions from any malignancy ≥2 years also exempted
19. Be breast feeding or pregnant, or plan to become pregnant while in the study
20. Be using an unreliable form of contraception (female subjects at risk of pregnancy only)
21. Be participating in another investigational drug study, parallel to, or within 4 weeks of Visit 0A
22. Have a known intolerance to mannitol or β2-agonists
23. Have uncontrolled hypertension - e.g. for adults: systolic blood pressure (BP) \> 190 and or diastolic BP \> 100
24. Subject has a condition or is 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
25. Have previously been screen failed for the study (exceptions - see section 3.3.2 Eligibility Criteria - Rescreening)
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Syntara

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Diana Bilton, MD

Role: PRINCIPAL_INVESTIGATOR

Brompton Hospital London UK

Greg Tino, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania Medical Centre, Philadelphia

Alan Barker, MD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health Sciences University, Portland Oregon

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

National Jewish Medical and Research Center

Denver, Colorado, United States

Site Status

University of Connecticut Health Center, Pulmonary Division

Farmington, Connecticut, United States

Site Status

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Florida Pulmonary Research

Winter Park, Florida, United States

Site Status

The University of Chicago Hospitals

Chicago, Illinois, United States

Site Status

Chest Medicine Clinical Services, LLC

Skokie, Illinois, United States

Site Status

Allergy and Critical Care Medicine Pulmonary Clinical Research Unit

Rochester, Minnesota, United States

Site Status

Saint Luke's Hospital

Chesterfield, Missouri, United States

Site Status

Pulmonary and Allergy Associates

Summit, New Jersey, United States

Site Status

Winthrop University Hospital

Mineola, New York, United States

Site Status

Research Associates of New York

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

The Oregon Clinic, PC/Pulmonary Division

Portland, Oregon, United States

Site Status

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

South Carolina Pharmaceutical Research

Spartanburg, South Carolina, United States

Site Status

Alamo Clinical Research Associates

San Antonio, Texas, United States

Site Status

Pulmonary Associates of Richmond, Inc

Richmond, Virginia, United States

Site Status

Hospital Zonal Especializado en Agudos y Cronicos "Dr Antonio A. Cetrangolo

Florida Partido de Vicente López, Buenos Aires, Argentina

Site Status

Centro Respiratorio Quilmes

Quilmes, Buenos Aires, Argentina

Site Status

Instituto Argentino de Investigación Neurológica

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Hospital Privado - Centro Medico de Cordoba

Córdoba, Córdoba Province, Argentina

Site Status

Insares

Mendoza, Mendoza Province, Argentina

Site Status

Centro Privado de Medicina Respiratoria

Entre Ríos, Paraná Entre Ríos, Argentina

Site Status

Hospital Interzonal General de Agudos "Dr Jose Penna"

Bahia Bianca, Provinica de Buenos Aires, Argentina

Site Status

Corporacion medica de General San Martin

Matheu, San Martin Provincia de Buenos Aires, Argentina

Site Status

Clinica del Torax

Rosario, Santa Fe Province, Argentina

Site Status

Instituto Cardiovascular de Rosario

Rosario, Santa Fe Province, Argentina

Site Status

Sanatorio Parque

Rosario, Santa Fe Province, Argentina

Site Status

Investigaciones en Patologias Respiratorias

San Miguel de Tucumán, Tucumán Province, Argentina

Site Status

Centro Médico Dra. De Salvo

Buenos Aires, , Argentina

Site Status

Atención Integral en Reumatología (AIR)

Buenos Aires, , Argentina

Site Status

Woolcock Institute of Medical Research

Glebe, New South Wales, Australia

Site Status

St George Hospital

Kogarah, New South Wales, Australia

Site Status

The Prince Charles Hospital

Chermside, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Repatriation General Hospital

Daws Park, South Australia, Australia

Site Status

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

Site Status

St Vincent's Hospital

Fitzroy, Victoria, Australia

Site Status

Western Hospital

Footscray, Victoria, Australia

Site Status

The Rooms of Dr C Steinfort

Geelong, Victoria, Australia

Site Status

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status

ULB Hopital Erasme - Department of Pneumology

Brussels, Brussels Capital, Belgium

Site Status

Cliniques Universitaires St. Luc (UCL) - Department of Pulmonology

Brussels, Brussels Capital, Belgium

Site Status

UZ Leuven (University Hospital Leuven) - Depatment of Pulmonary Medicine

Leuven, Leuven, Belgium

Site Status

Pontificia Universidad Catolica de Chile

Santiago, Santiago Metropolitan, Chile

Site Status

Universidad de Chile

Santiago, Santiago Metropolitan, Chile

Site Status

Hospital Regional de Talca

Talca, Talca, Chile

Site Status

IKF Pneumologie GmbH and Co KG

Frankfurt am Main, Hesse, Germany

Site Status

Medizinische Hochschule Hannover Klinik für Pneumologie

Hanover, Lower Saxony, Germany

Site Status

Lungen und Bronchialheikunde

Bonn, North Rhine-Westphalia, Germany

Site Status

Pneumologisch Studienzentrum

Leipzig, Saxony, Germany

Site Status

Medisch Centrum Alkmaar - Department of Pulmonary Medicine

Alkmaar, Alkmaar AM, Netherlands

Site Status

Atrium MC -Department of Pulmonary Diseases

Heerlen, Heerlen, Netherlands

Site Status

Medisch Centrum Leeuwarden (MCL) - Department of Pulmonology

Leeuwarden, Leeuwarden AD, Netherlands

Site Status

Middlemore Hospital

Auckland, Auckland, New Zealand

Site Status

Green Lane Clinical Centre

Greenlane, Auckland, New Zealand

Site Status

Waikato Hospital

Hamilton, , New Zealand

Site Status

West Wales General Hospital

Carmarthen, Carmarthenshire, United Kingdom

Site Status

Royal Derby Hospital

Derby, Derbyshire, United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, Devon, United Kingdom

Site Status

Torbay Hospital

Torquay, Devon, United Kingdom

Site Status

Castle Hill Hospital

Cottingham, East Yorkshire, United Kingdom

Site Status

Glenfield Hospital

Leicester, Leicestershire, United Kingdom

Site Status

Nottingham City Hospital

Nottingham, Nottinghamshire, United Kingdom

Site Status

Churchill Hospital

Headington, Oxfordshire, United Kingdom

Site Status

Royal Shrewsbury Hospital

Shrewsbury, Shropshire, United Kingdom

Site Status

Sheffield Northern General Hospital

Sheffield, South Yorkshire, United Kingdom

Site Status

Stafford Hospital

Stafford, Staffordshire, United Kingdom

Site Status

Ashford & St Peters Hospital

Chertsey, Surrey, United Kingdom

Site Status

University Hospital of North Tees

Stockton, Teeside, United Kingdom

Site Status

Llandough Hospital

Cardiff, Vale of Glamorgan, United Kingdom

Site Status

Birmingam Queen Elizabeth Hospital

Birmingham, West Midlands, United Kingdom

Site Status

Wolverhampton New Cross Hospital

Wolverhampton, West Midlands, United Kingdom

Site Status

Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status

Belfast City Hospital

Belfast, , United Kingdom

Site Status

University Hospital Aintree

Liverpool, , United Kingdom

Site Status

Royal Brompton Hospital

London, , United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

North Tyneside General Hospital

North Shields, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Wrexham Maelor Hospital

Wrexham, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Australia Belgium Chile Germany Netherlands New Zealand United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Daviskas E, Anderson SD, Eberl S, Chan HK, Bautovich G. Inhalation of dry powder mannitol improves clearance of mucus in patients with bronchiectasis. Am J Respir Crit Care Med. 1999 Jun;159(6):1843-8. doi: 10.1164/ajrccm.159.6.9809074.

Reference Type BACKGROUND
PMID: 10351929 (View on PubMed)

Daviskas E, Anderson SD, Eberl S, Young IH. Effect of increasing doses of mannitol on mucus clearance in patients with bronchiectasis. Eur Respir J. 2008 Apr;31(4):765-72. doi: 10.1183/09031936.00119707. Epub 2007 Dec 5.

Reference Type BACKGROUND
PMID: 18057051 (View on PubMed)

Daviskas E, Anderson SD, Young IH. Inhaled mannitol changes the sputum properties in asthmatics with mucus hypersecretion. Respirology. 2007 Sep;12(5):683-91. doi: 10.1111/j.1440-1843.2007.01107.x.

Reference Type BACKGROUND
PMID: 17875056 (View on PubMed)

Daviskas E, Anderson SD. Hyperosmolar agents and clearance of mucus in the diseased airway. J Aerosol Med. 2006 Spring;19(1):100-9. doi: 10.1089/jam.2006.19.100.

Reference Type BACKGROUND
PMID: 16551221 (View on PubMed)

Daviskas E, Anderson SD, Gomes K, Briffa P, Cochrane B, Chan HK, Young IH, Rubin BK. Inhaled mannitol for the treatment of mucociliary dysfunction in patients with bronchiectasis: effect on lung function, health status and sputum. Respirology. 2005 Jan;10(1):46-56. doi: 10.1111/j.1440-1843.2005.00659.x.

Reference Type BACKGROUND
PMID: 15691238 (View on PubMed)

Daviskas E, Robinson M, Anderson SD, Bye PT. Osmotic stimuli increase clearance of mucus in patients with mucociliary dysfunction. J Aerosol Med. 2002 Fall;15(3):331-41. doi: 10.1089/089426802760292681.

Reference Type BACKGROUND
PMID: 12396422 (View on PubMed)

Daviskas E, Anderson SD, Eberl S, Chan HK, Young IH. The 24-h effect of mannitol on the clearance of mucus in patients with bronchiectasis. Chest. 2001 Feb;119(2):414-21. doi: 10.1378/chest.119.2.414.

Reference Type BACKGROUND
PMID: 11171717 (View on PubMed)

Bilton D, Tino G, Barker AF, Chambers DC, De Soyza A, Dupont LJ, O'Dochartaigh C, van Haren EH, Vidal LO, Welte T, Fox HG, Wu J, Charlton B; B-305 Study Investigators. Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial. Thorax. 2014 Dec;69(12):1073-9. doi: 10.1136/thoraxjnl-2014-205587. Epub 2014 Sep 21.

Reference Type DERIVED
PMID: 25246664 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

DPM-B-305

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

The Leaky Lung Test
NCT02306473 COMPLETED EARLY_PHASE1