Clinical trial NCT00630812: Long Term Administration of Inhaled Mannitol in Cystic Fibrosis
Official title: Long Term Administration of Inhaled Mannitol in Cystic Fibrosis- A Safety and Efficacy Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
mannitol
mucoactive
Lead sponsor: Syntara
Sponsor class: INDUSTRY
Collaborators: name: ethica Clinical Research Inc.
name: Europe: KasaConsult bvba, Hoegaarden, Belgium
name: Resolution Latin America
First posted: 2008-03-07
Enrollment: 318
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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'

    -

Primary outcomes:
measure: Change in Absolute FEV1 From Baseline Over 26 Weeks
timeFrame: 26 weeks
Secondary outcomes:
measure: Change in FEV1 From Baseline Over 26 Weeks - Dornase Users
timeFrame: 26 weeks
measure: Rate of Protocol Defined Pulmonary Exacerbations (PDPE)
timeFrame: 26 weeks
measure: Hospitalisations Associated With Protocol Defined Pulmonary Exacerbations (PDPEs)
timeFrame: 26 weeks
measure: Antibiotic Use Associated With PDPEs
timeFrame: 26 weeks
measure: Absolute Change in FEV1 Percent Predicted at 26 Weeks
timeFrame: 26 weeks
measure: Change in FVC (mL) Across 26 Weeks
timeFrame: 26 weeks
measure: Change From Baseline FEF25-75 (mL/s) Over 26 Weeks
timeFrame: 26 weeks
measure: Sputum Weight at Baseline in Response to First Dose of Treatment
timeFrame: up to 30 mins after first dose of trial treatment
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Hartford
country: United States
facility: Central Connecticut Cystic Fibrosis Center
state: Connecticut
city: Jacksonville
country: United States
facility: Nemours Childrens Clinic
state: Florida
city: Miami
country: United States
facility: Batchelor Children's Research Institute - University of Miami
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic Orlando
state: Florida
city: Idaho
country: United States
facility: St Lukes CF Center of Idaho
state: Idaho
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Portland
country: United States
facility: Maine Pediatric Specialty Group
state: Maine
city: Baltimore
country: United States
facility: John Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Omaha
country: United States
facility: Nebraska Medical Center - Nebraska Regional CF Center
state: Nebraska
city: Buffalo
country: United States
facility: Women and Childrens Hospital of Buffalo
state: New York
city: Toledo
country: United States
facility: The Toledo Hospital and Toledo Childrens Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: St Christopher's Hospital for Children
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of SC
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Children's Specialty Clinic
state: South Dakota
city: Memphis
country: United States
facility: Le Bonheur Children's Medical Center
state: Tennessee
city: Austin
country: United States
facility: Children's Chest Associates of Austin
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Alamo Clinical Research Associates
state: Texas
city: San Antonio
country: United States
facility: Christus Santa Rosa Children's Hospital Cystic Fibrosis Center
state: Texas
city: Richmond
country: United States
facility: Pediatric Research, VCU Medical Centre
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington medical centre
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Bahia Blanca
country: Argentina
facility: Hospital Interzonal Dr Jose Penna Bahia Blanca
state: Buenos Aires
city: Caba
country: Argentina
facility: Hospital de Ninos Dr Ricardo Gutierrez, Pediatria
state: Buenos Aires
city: Ciudad Autonoma
country: Argentina
facility: Hospital Gral. de Ninos Pedro de Elizalde
state: Buenos Aires
city: La Plata
country: Argentina
facility: Hospital de Ninos Superiora Sor Maria Ludovica de La Plata
state: Buenos Aires
city: Guaymallen
country: Argentina
facility: Hospital Pediatrico Dr Humberto J Notti
state: Mendosa
city: Buenos Aires
country: Argentina
facility: Atención Integral en Reumatologia (AIR)
city: Cordoba
country: Argentina
facility: Clinica Universitaria Privada Reina Fabiola - Universidad Cotolica de Cordoba
city: Cordoba
country: Argentina
facility: Hospital de Ninos del la Santisima Trinidad
city: Edegem
country: Belgium
facility: Pediatrics Respiratory Medicine
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Hopital Universitaire Reine Fabiola
state: Brussel
city: Brussel
country: Belgium
facility: UZ Brussel Laarbeeklan 101
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Calgary
country: Canada
facility: Foothills medical center
state: Alberta
city: Halifax
country: Canada
facility: QEII Health Sciences Center
state: Nova Scotia
city: London
country: Canada
facility: The Children's Asthma Clinic
state: Ontario
city: Nantes
country: France
facility: Hopital Mere-Enfant
state: Cedex
city: Le Chesnay
country: France
facility: Hopital Andre Mignot
state: Cedix
city: Lille CEDEX
country: France
facility: Hopital Jeanne de Flandre
state: Lille
city: Bron Cedex
country: France
facility: Hopital Femme-Mere-Enfents
state: Lyon
city: Strasbourg CEDEX
country: France
facility: Hopital de Hautepierre
state: Strasbourg
city: Paris
country: France
facility: Hopital Robert Debre
city: Munchen
country: Germany
facility: University of Munich Medizinischen Klinik Innenstadt
city: Tubingen
country: Germany
facility: Universitats Kinderklinik Tubungen Wurzburg
city: Wurzburg
country: Germany
facility: Universitats Kinderklinik Wurzburg
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre
Study officials:
affiliation: University of Washington Medical Centre, Seattle WA
name: Moira L Aitken, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol. 2002 Apr;33(4):293-306. doi: 10.1002/ppul.10079.
citation: 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.
citation: 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. doi: 10.1034/j.1399-3003.1999.14c30.x.
citation: 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.
citation: 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. doi: 10.1183/09031936.97.10112449.
citation: Jaques A, Daviskas E, Turton JA, McKay K, Cooper P, Stirling RG, Robertson CF, Bye PTP, LeSouef PN, Shadbolt B, Anderson SD, Charlton B. Inhaled mannitol improves lung function in cystic fibrosis. Chest. 2008 Jun;133(6):1388-1396. doi: 10.1378/chest.07-2294. Epub 2008 Mar 13.
citation: Nevitt SJ, Thornton J, Murray CS, Dwyer T. Inhaled mannitol for cystic fibrosis. Cochrane Database Syst Rev. 2020 May 1;5(5):CD008649. doi: 10.1002/14651858.CD008649.pub4.
citation: 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. doi: 10.1164/rccm.201109-1666OC. Epub 2011 Dec 28.