Long Term Administration of Inhaled Mannitol in Cystic Fibrosis - Full Text View

Purpose

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.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: inhaled mannitol Drug: Placebo comparator	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Long Term Administration of Inhaled Mannitol in Cystic Fibrosis- A Safety and Efficacy Study

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Mannitol

U.S. FDA Resources

Further study details as provided by Pharmaxis:

Primary Outcome Measures:

Change in absolute FEV1 [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]

Enrollment:	318
Study Start Date:	September 2008
Study Completion Date:	November 2010
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A active treatment	Drug: inhaled mannitol 400 mg BD for 26 + 26 weeks
Placebo Comparator: B	Drug: Placebo comparator BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase

Eligibility

Ages Eligible for Study:	6 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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.
Be considered "terminally ill" or eligible for lung transplantation
Have had a lung transplant
Be using nebulized hypertonic saline in the 4 weeks prior to visit 1
Have had a significant episode of hemoptysis (>60 mL) in the three months prior to enrolment
Have had a myocardial infarction in the three months prior to enrolment
Have had a cerebral vascular accident in the three months prior to enrolment
Have had major ocular surgery in the three months prior to enrolment
Have had major abdominal, chest or brain surgery in the three months prior to enrolment
Have a known cerebral, aortic or abdominal aneurysm
Be breast feeding or pregnant, or plan to become pregnant while in the study
Be using an unreliable form of contraception (female subjects at risk of pregnancy only)
Be participating in another investigative drug study, parallel to, or within 4 weeks of visit 0
Have a known allergy to mannitol
Be using beta blockers
Have uncontrolled hypertension - systolic BP > 190 and / or diastolic BP > 100
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
Be 'Mannitol Tolerance Test positive'

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Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00630812

Show 53 Study Locations

Sponsors and Collaborators

Pharmaxis

ethica Clinical Research Inc.

Europe: KasaConsult bvba, Hoegaarden, Belgium

Argentina: Resolution Latin America; Buenos Aires, Argentina

Investigators

Principal Investigator:

Moira L Aitken, MD

University of Washington Medical Centre, Seattle WA

More Information

Publications:

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

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.

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. Review.

Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol. 2002 Apr;33(4):293-306. Review.

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.

Robinson M, Daviskas E, Eberl S, Baker J, Chan HK, Anderson SD, Bye PT. The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study. Eur Respir J. 1999 Sep;14(3):678-85.

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.

Daviskas E, Anderson SD, Brannan JD, Chan HK, Eberl S, Bautovich G. Inhalation of dry-powder mannitol increases mucociliary clearance. Eur Respir J. 1997 Nov;10(11):2449-54.

Jaques A, Daviskas E, Turton JA, McKay K, Cooper P, Stirling RG, Robertson CF, Bye PT, Lesouëf PN, Shadbolt B, Anderson SD, Charlton B. Inhaled mannitol improves lung function in cystic fibrosis. Chest. 2008 Jun;133(6):1388-96. Epub 2008 Mar 13.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Aitken ML, Bellon G, De Boeck K, Flume PA, Fox HG, Geller DE, Haarman EG, Hebestreit HU, Lapey A, Schou IM, Zuckerman JB, Charlton B; CF302 Investigators. Long-term inhaled dry powder mannitol in cystic fibrosis: an international randomized study. Am J Respir Crit Care Med. 2012 Mar 15;185(6):645-52. Epub 2011 Dec 28.

Responsible Party:	Pharmaxis
ClinicalTrials.gov Identifier:	NCT00630812 History of Changes
Other Study ID Numbers:	DPM-CF-302
Study First Received:	February 27, 2008
Last Updated:	August 6, 2012
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Germany: Federal Institute for Drugs and Medical Devices Belgium: Federal Agency for Medicinal Products and Health Products Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Pharmaxis:

cystic fibrosis
mannitol
mucoactive

Additional relevant MeSH terms:

Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

Mannitol
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2013