Long Term Administration of Inhaled Mannitol in Cystic Fibrosis

NCT00630812 | Completed Phase 3 Results DMC

• 1 other identifier: DPM-CF-302
• Study Type: interventional
• Target: 318
• Locations: 7 countries
• Sites: 53

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.

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; mannitol; mucoactive

Outcome Measures

Primary Outcomes (1)

• Change in Absolute FEV1 From Baseline Over 26 Weeks

  Change from baseline in forced expiratory volume at one second (FEV1) averaged over 26 weeks (measured at 6,14 and 26 weeks) The mean absolute change from baseline FEV1 (mL) over 26 weeks (measured at week 6, 14 and 26) will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach.Least square means presented are for the average change over the 6, 14, and 26 week visits.

  26 weeks

Secondary Outcomes (8)

• Change in FEV1 From Baseline Over 26 Weeks - Dornase Users

  26 weeks

• Rate of Protocol Defined Pulmonary Exacerbations (PDPE)

  26 weeks

• Hospitalisations Associated With Protocol Defined Pulmonary Exacerbations (PDPEs)

  26 weeks

• Antibiotic Use Associated With PDPEs

  26 weeks

• Absolute Change in FEV1 Percent Predicted at 26 Weeks

  26 weeks

Study Arms (2)

A

EXPERIMENTAL

active treatment

Drug: inhaled mannitol

B

PLACEBO COMPARATOR

Drug: Placebo comparator

Interventions

inhaled mannitol DRUG

400 mg BD for 26 + 26 weeks

A

Placebo comparator DRUG

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

B

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Syntara: lead
• ethica Clinical Research Inc.: collaborator
• Europe: KasaConsult bvba, Hoegaarden, Belgium: collaborator
• Resolution Latin America: collaborator

Study Sites (53)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Central Connecticut Cystic Fibrosis Center

Hartford, Connecticut, 66106, United States

Location

Nemours Childrens Clinic

Jacksonville, Florida, 32207, United States

Location

Batchelor Children's Research Institute - University of Miami

Miami, Florida, 33136, United States

Location

Nemours Children's Clinic Orlando

Orlando, Florida, 32801, United States

Location

St Lukes CF Center of Idaho

Idaho City, Idaho, 83712, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Louisiana State University Health Sciences Center

Shreveport, Louisiana, 71130-3932, United States

Location

Maine Pediatric Specialty Group

Portland, Maine, 4102, United States

Location

John Hopkins

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 62114, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

Nebraska Medical Center - Nebraska Regional CF Center

Omaha, Nebraska, 68198-5300, United States

Location

Women and Childrens Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

The Toledo Hospital and Toledo Childrens Hospital

Toledo, Ohio, 43606, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

St Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Medical University of SC

Charleston, South Carolina, 29425, United States

Location

Sanford Children's Specialty Clinic

Sioux Falls, South Dakota, 57117, United States

Location

Le Bonheur Children's Medical Center

Memphis, Tennessee, 38105, United States

Location

Children's Chest Associates of Austin

Austin, Texas, 78723, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Alamo Clinical Research Associates

San Antonio, Texas, 78212, United States

Location

Christus Santa Rosa Children's Hospital Cystic Fibrosis Center

San Antonio, Texas, 78229-3900, United States

Location

Pediatric Research, VCU Medical Centre

Richmond, Virginia, 23298, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Washington medical centre

Seattle, Washington, 58103, United States

Location

University of Wisconsin

Madison, Wisconsin, 53972, United States

Location

Hospital Interzonal Dr Jose Penna Bahia Blanca

Bahía Blanca, Buenos Aires, 8000, Argentina

Location

Hospital de Ninos Dr Ricardo Gutierrez, Pediatria

CABA, Buenos Aires, C1425EFD, Argentina

Location

Hospital Gral. de Ninos Pedro de Elizalde

Ciudad Autonoma, Buenos Aires, C1270AAN, Argentina

Location

Hospital de Ninos Superiora Sor Maria Ludovica de La Plata

La Plata, Buenos Aires, 1900, Argentina

Location

Hospital Pediatrico Dr Humberto J Notti

Villa Nueva, Mendoza Province, 5519, Argentina

Location

Atención Integral en Reumatologia (AIR)

Buenos Aires, C1426AAL, Argentina

Location

Clinica Universitaria Privada Reina Fabiola - Universidad Cotolica de Cordoba

Córdoba, 5000, Argentina

Location

Hospital de Ninos del la Santisima Trinidad

Córdoba, 5000, Argentina

Location

Pediatrics Respiratory Medicine

Edegem, Antwerpen, 2650, Belgium

Location

Hopital Universitaire Reine Fabiola

Brussels, Brussels Capital, 1090, Belgium

Location

UZ Brussel Laarbeeklan 101

Brussels, 1090, Belgium

Location

UZ Gasthuisberg

Leuven, 3000, Belgium

Location

Foothills medical center

Calgary, Alberta, T2N4N1, Canada

Location

QEII Health Sciences Center

Halifax, Nova Scotia, B3H3A7, Canada

Location

The Children's Asthma Clinic

London, Ontario, N6A1V2, Canada

Location

Hopital Mere-Enfant

Nantes, Cedex, 44093, France

Location

Hopital Andre Mignot

Le Chesnay, Cedix, 78157, France

Location

Hopital Jeanne de Flandre

Lille, Lille, 59037, France

Location

Hopital Femme-Mere-Enfents

Bron, Lyon, 69677, France

Location

Hopital de Hautepierre

Strasbourg, Strasbourg, 67098, France

Location

Hopital Robert Debre

Paris, 75019, France

Location

University of Munich Medizinischen Klinik Innenstadt

München, 80336, Germany

Location

Universitats Kinderklinik Tubungen Wurzburg

Tübingen, 72076, Germany

Location

Universitats Kinderklinik Wurzburg

Würzburg, 97080, Germany

Location

Academic Medical Centre

Amsterdam, 1100DD, Netherlands

Location

Related Publications (11)

• 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.

  PMID: 16551221 BACKGROUND

• 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.

  PMID: 15691238 BACKGROUND

• 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.

  PMID: 12396422 BACKGROUND

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

  PMID: 11921459 BACKGROUND

• 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.

  PMID: 11171717 BACKGROUND

• 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.

  PMID: 10543292 BACKGROUND

• 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.

  PMID: 10351929 BACKGROUND

• 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.

  PMID: 9426077 BACKGROUND

• 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.

  PMID: 18339790 BACKGROUND

• 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.

  PMID: 32358807 DERIVED

• 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.

  PMID: 22198974 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Brett Charlton
• Organization: Pharmaxis

Brett.Charlton@pharmaxis.com.au

02 94547210

Study Officials

• Moira L Aitken, MD

  University of Washington Medical Centre, Seattle WA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2008
• First Posted: March 7, 2008
• Study Start: September 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: November 1, 2010
• Last Updated: October 9, 2020
• Results First Posted: October 9, 2020

Record last verified: 2020-10

Locations

CA (3); AR (8); BE (4); US (28); FR (6); DE (3); NL (1)