Long Term Administration of Inhaled Mannitol in Cystic Fibrosis

NCT ID: NCT00630812

Last Updated: 2020-10-09

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

318 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-30

Study Completion Date

2010-11-30

Brief Summary

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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

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Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A

active treatment

Group Type EXPERIMENTAL

inhaled mannitol

Intervention Type DRUG

400 mg BD for 26 + 26 weeks

B

Group Type PLACEBO_COMPARATOR

Placebo comparator

Intervention Type DRUG

BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase

Interventions

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inhaled mannitol

400 mg BD for 26 + 26 weeks

Intervention Type DRUG

Placebo comparator

BD for 26 weeks followed by 26 weeks of inhaled mannitol in the open label phase

Intervention Type DRUG

Eligibility Criteria

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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'

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Minimum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ethica Clinical Research Inc.

INDUSTRY

Sponsor Role collaborator

Europe: KasaConsult bvba, Hoegaarden, Belgium

INDUSTRY

Sponsor Role collaborator

Resolution Latin America

OTHER

Sponsor Role collaborator

Syntara

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Moira L Aitken, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington Medical Centre, Seattle WA

Locations

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University of Arizona

Tucson, Arizona, United States

Site Status

Central Connecticut Cystic Fibrosis Center

Hartford, Connecticut, United States

Site Status

Nemours Childrens Clinic

Jacksonville, Florida, United States

Site Status

Batchelor Children's Research Institute - University of Miami

Miami, Florida, United States

Site Status

Nemours Children's Clinic Orlando

Orlando, Florida, United States

Site Status

St Lukes CF Center of Idaho

Idaho City, Idaho, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Louisiana State University Health Sciences Center

Shreveport, Louisiana, United States

Site Status

Maine Pediatric Specialty Group

Portland, Maine, United States

Site Status

John Hopkins

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Missouri

Columbia, Missouri, United States

Site Status

Nebraska Medical Center - Nebraska Regional CF Center

Omaha, Nebraska, United States

Site Status

Women and Childrens Hospital of Buffalo

Buffalo, New York, United States

Site Status

The Toledo Hospital and Toledo Childrens Hospital

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

St Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Medical University of SC

Charleston, South Carolina, United States

Site Status

Sanford Children's Specialty Clinic

Sioux Falls, South Dakota, United States

Site Status

Le Bonheur Children's Medical Center

Memphis, Tennessee, United States

Site Status

Children's Chest Associates of Austin

Austin, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Alamo Clinical Research Associates

San Antonio, Texas, United States

Site Status

Christus Santa Rosa Children's Hospital Cystic Fibrosis Center

San Antonio, Texas, United States

Site Status

Pediatric Research, VCU Medical Centre

Richmond, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

University of Washington medical centre

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Hospital Interzonal Dr Jose Penna Bahia Blanca

Bahía Blanca, Buenos Aires, Argentina

Site Status

Hospital de Ninos Dr Ricardo Gutierrez, Pediatria

CABA, Buenos Aires, Argentina

Site Status

Hospital Gral. de Ninos Pedro de Elizalde

Ciudad Autonoma, Buenos Aires, Argentina

Site Status

Hospital de Ninos Superiora Sor Maria Ludovica de La Plata

La Plata, Buenos Aires, Argentina

Site Status

Hospital Pediatrico Dr Humberto J Notti

Villa Nueva, Mendoza Province, Argentina

Site Status

Atención Integral en Reumatologia (AIR)

Buenos Aires, , Argentina

Site Status

Clinica Universitaria Privada Reina Fabiola - Universidad Cotolica de Cordoba

Córdoba, , Argentina

Site Status

Hospital de Ninos del la Santisima Trinidad

Córdoba, , Argentina

Site Status

Pediatrics Respiratory Medicine

Edegem, Antwerpen, Belgium

Site Status

Hopital Universitaire Reine Fabiola

Brussels, Brussels Capital, Belgium

Site Status

UZ Brussel Laarbeeklan 101

Brussels, , Belgium

Site Status

UZ Gasthuisberg

Leuven, , Belgium

Site Status

Foothills medical center

Calgary, Alberta, Canada

Site Status

QEII Health Sciences Center

Halifax, Nova Scotia, Canada

Site Status

The Children's Asthma Clinic

London, Ontario, Canada

Site Status

Hopital Mere-Enfant

Nantes, Cedex, France

Site Status

Hopital Andre Mignot

Le Chesnay, Cedix, France

Site Status

Hopital Jeanne de Flandre

Lille, Lille, France

Site Status

Hopital Femme-Mere-Enfents

Bron, Lyon, France

Site Status

Hopital de Hautepierre

Strasbourg, Strasbourg, France

Site Status

Hopital Robert Debre

Paris, , France

Site Status

University of Munich Medizinischen Klinik Innenstadt

München, , Germany

Site Status

Universitats Kinderklinik Tubungen Wurzburg

Tübingen, , Germany

Site Status

Universitats Kinderklinik Wurzburg

Würzburg, , Germany

Site Status

Academic Medical Centre

Amsterdam, , Netherlands

Site Status

Countries

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United States Argentina Belgium Canada France Germany Netherlands

References

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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)

Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol. 2002 Apr;33(4):293-306. doi: 10.1002/ppul.10079.

Reference Type BACKGROUND
PMID: 11921459 (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)

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.

Reference Type BACKGROUND
PMID: 10543292 (View on PubMed)

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, 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.

Reference Type BACKGROUND
PMID: 9426077 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18339790 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32358807 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22198974 (View on PubMed)

Other Identifiers

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DPM-CF-302

Identifier Type: -

Identifier Source: org_study_id

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