A Safety and Efficacy Trial of Inhaled Mannitol in Adult Cystic Fibrosis Subjects

NCT ID: NCT02134353

Last Updated: 2020-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 423 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2017-02-28

Brief Summary

This trial aims to provide prospective evidence of the safety and efficacy of mannitol 400 mg b.i.d. in subjects aged 18 years and above.

We hypothesize that inhaled mannitol 400 mg b.i.d. will increase the mean change from baseline FEV1 (mL) compared to control over the 26-week treatment period in adult subjects with cystic fibrosis. Any improvement in FEV1 is considered clinically meaningful, however, this trial has set a threshold of 80 mL for the purposes of determining an appropriate sample size for statistical power while retaining trial feasibility in an orphan disease population

Detailed Description

This is a double-blind, randomized, parallel arm, controlled, multicenter, and interventional clinical trial. Potential subjects will sign the informed consent form (ICF) and be assessed for eligibility. After satisfying all inclusion & exclusion criteria, subjects will be given a mannitol tolerance test (MTT). Those subjects that pass the MTT will be randomized to receive inhaled mannitol (400 mg b.i.d.) or control b.i.d. for a period of 26-weeks.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental arm A

Active treatment. Inhaled Mannitol

Group Type: EXPERIMENTAL

Inhaled mannitol

Intervention Type: DRUG

Inhaled mannitol 400 mg BD for 26 weeks

Arm B - Control

Arm B

Group Type: PLACEBO_COMPARATOR

Placebo Comparator: Arm B - Control

Intervention Type: DRUG

Placebo Comparator: Arm B - Control BD for 26 weeks

Interventions

Inhaled mannitol

Inhaled mannitol 400 mg BD for 26 weeks

Intervention Type: DRUG

Placebo Comparator: Arm B - Control

Placebo Comparator: Arm B - Control BD for 26 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Have given written informed consent to participate in this trial 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 at least 18 years old;

4. Have FEV1 > 40 % and < 90% predicted (using NHanes III [1]);

5. Be able to perform all the techniques necessary to measure lung function;

6. Be adherent with maintenance therapies (antibiotics and or rhDNase), if used, for at least 80% of the time in the two weeks prior to visit 1 and

7. If rhDNase and/or maintenance antibiotic are being used treatment must have been established at least 1 month prior to screening (Visit 0). The subject should remain on the rhDNase and / or maintenance antibiotics for the duration of the trial. The subject should not commence treatment with rhDNase or maintenance antibiotics during the trial

Exclusion Criteria

1. Be investigators, site personnel directly affiliated with this trial, 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 maintenance nebulized hypertonic saline in the 2 weeks prior to visit 1;

5. Have had a significant episode of hemoptysis (> 60 mL) in the three months prior to Visit 0;

6. Have had a myocardial infarction in the three months prior to Visit 0;

7. Have had a cerebral vascular accident in the three months prior to Visit 0;

8. Have had major ocular surgery in the three months prior to Visit 0;

9. Have had major abdominal, chest or brain surgery in the three months prior to Visit 0;

10. Have a known cerebral, aortic or abdominal aneurysm;

11. Be breast feeding or pregnant, or plan to become pregnant while in the trial;

12. Be using an unreliable form of contraception (female subjects at risk of pregnancy only);

13. Be participating in another investigative drug trial, parallel to, or within 4 weeks of screening (Visit 0);

14. Have a known allergy to mannitol;

15. Be using non-selective oral beta blockers;

16. Have uncontrolled hypertension -i.e. 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 subject's participation in the trial;or

18. Have a failed or incomplete MTT at trial entry (as evaluated in Section 8.1.1.1).

19. The subject must not commence treatment with rhDNase or maintenance antibiotics during the trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Syntara

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Moira Aitken, MD

Role: PRINCIPAL_INVESTIGATOR

Brett Charlton, MD

Role: STUDY_DIRECTOR

Medical Director

Locations

Dr Lawrence Sinde

Mobile, Alabama, United States

University of Arizona

Tucson, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Pediatric Pulmonology

Long Beach, California, United States

University of CA, Davis

Sacramento, California, United States

Hartford Hospital

Hartford, Connecticut, United States

Dr Mitchell Rothstein

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

Central Florida Pulmonary Group, P.A.

Orlando, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

Cystic Fibrosis Center of Chicago

Glenview, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Illinois Lung Institute

Peoria, Illinois, United States

University of Kansas Hospital

Kansas City, Kansas, United States

Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, United States

John Hopkins

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Spectrum Health Offices of Research Administration

Grand Rapids, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Dr Joseph Ojile

St Louis, Missouri, United States

Dartmouth-Hitchcock Specialty Care

Bedford, New Hampshire, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

The Cystic Fibrosis Center Beth Israel Medical Center

New York, New York, United States

Dr Allen Dozor

Valhalla, New York, United States

Akron Children's Hospital

Akron, Ohio, United States

University of Cincinnati

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

The Children's Medical Center of Dayton

Dayton, Ohio, United States

The Toledo Hospital and Toledo Childrens Hospital

Toledo, Ohio, United States

Pediatric Pulmonary & CF Center

Oklahoma City, Oklahoma, United States

Dr Santiago Reyes

Oklahoma City, Oklahoma, United States

Pediatric Clinic

Portland, Oregon, United States

Medical University of SC

Charleston, South Carolina, United States

One Richland Medical Park

Columbia, South Carolina, United States

University of Washington

Seattle, Washington, United States

Insares

Mendoza, Mendoza Province, Argentina

Hospital Interzonal General de Agudos Dr. Jose Penna

Bahía Blanca, , Argentina

Hospital del Tórax Cetrángolo

Buenos Aires, , Argentina

Hospital Regional Español de Bahía Blanca

Buenos Aires, , Argentina

Hospital San Roque

Córdoba, , Argentina

Mater Adult Hospital

Brisbane, Queensland, Australia

UZ VUB

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

CHR Citadelle

Liège, , Belgium

QEII Health Sciences Center

Halifax, , Canada

Institut de recherches cliniques de Montréal

Montreal, , Canada

The Ottawa Hospital, General Campus

Ottawa, , Canada

FN Brno

Brno, , Czechia

Országos Korányi Tbc

Budapest, , Hungary

Klinikai Farmakológiai Központ

Debrecen, , Hungary

Mosdós Tüdőgyógyintézet

Mosdós, , Hungary

Törökbálint Tüdőgyógyintézet

Törökbálint, , Hungary

Pediatrics Pulmonary Department Rambam Healthcare Campus

Haifa, , Israel

Schneider Children's Medical Center of Israel

Petah Tikva, , Israel

Spedali Civili Brescia

Brescia, , Italy

IRCCS Ca' Granda Ospedale Maggiore Policlinico Mil

Milan, , Italy

AOU San Luigi Gonzaga

Orbassano, , Italy

Aziendao Spedaliera Universitaria

Parma, , Italy

Cystic Fibrosis Center Hospital San Carlo

Potenza, , Italy

Centro Fibrosi Cistica Policlinico Umberto I

Roma, , Italy

Azienda Ospedaliera Universitaria Integratadi Verona

Verona, , Italy

Instituto Jaliscience de Investigacion Clinica

Guadalajara, , Mexico

Unidad Médica de Occidente

Guadalajara, , Mexico

Arke Estudios Clinicos S.A

Mexico City, , Mexico

CEPREP- Hospital Universitario

Monterrey, , Mexico

Greenlane Hospital

Auckland, , New Zealand

Canterbury Respiratory Research Group

Christchurch, , New Zealand

Otago Respiratory Research Unit, Dunedin Hospital

Dunedin, , New Zealand

Szpital Dziecięcy Polanki im. M. Płażyńskiego w Gdańsku sp.

Gdansk, , Poland

Centrum Medyczne Karpacz SA

Karpacz, , Poland

Wojewodzki Specjalistyczny Szpital Dzieciecy im. W. Buszkowskiego

Kielce, , Poland

Wojewodzki Szpital Specjalistyczny im.

Lodz, , Poland

Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu

Poznan, , Poland

Sanatorium Cassia-Villa Medica S.C.

Rabka-Zdrój, , Poland

Podkarpacki Osrodek Pulmonologii i Alergologii

Rzeszów, , Poland

Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"

Bucharest, , Romania

Institutul de Pneumoftiziologie "Marius Nasta" Bucuresti, Sectia Clinica Pneumologie V

Bucharest, , Romania

Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca

Cluj-Napoca, , Romania

Spitalul Clinic de Pneumoftiziologie Lasi

Lasi, , Romania

Tatiana I. Martynenko

Barnaul, , Russia

Pulmonology Research Institute

Moscow, , Russia

Research and Clinical Center of interstitial and orphan lung diseases

Saint Petersburg, , Russia

Mikhail Smirnov

Vladimir, , Russia

Clinical Hospital# 2

Yaroslavl, , Russia

Oddelenie pneumológie a ftizeológie

Banská Bystrica, , Slovakia

Imuno-alergologická ambulancia

Bratislava, , Slovakia

Detská fakultná nemocnica Košice

Košice, , Slovakia

University of Cape Town Lung Institute

Cape Town, , South Africa

St. Augustine's Medical Centre 2

Durban, , South Africa

Hospital Universitario Virgen de la Arrixaca

El Palmar, , Spain

Hospital Universitaro La Paz

Madrid, , Spain

Hospital Universitario Central de Asturias

Oviedo, , Spain

Hospital Virgen del Rocio Hospital Unidad de Fibrosis Quistica

Seville, , Spain

Hospital Universitario La Fe Neumología

Valencia, , Spain

Dnipropetrovsk State Medical Academy, Faculty Theraphy and Endocrinology Chair

Dnipropetrovsk, , Ukraine

Municipal Institution "Kherson City Clinical Hospital n.a. Afanasiy and Olha Tropin

Kherson, , Ukraine

Kremenchuk First City Hospital n.a. O.T.Bogaevskyy

Kremenchuk, , Ukraine

Department of Pulmonology and Thoracic Surgery of Public Institution " Kryvyy Rig City Clinical Hospital # 8

Kryvyy Rig, , Ukraine

Hospital Department of Municipal Institution "Zaporizhzhya Regional Clinical Hospital"

Zaporizhzhya, , Ukraine

Countries

United States; Argentina; Australia; Belgium; Canada; Czechia; Hungary; Israel; Italy; Mexico; New Zealand; Poland; Romania; Russia; Slovakia; South Africa; Spain; Ukraine

References

Flume PA, Amelina E, Daines CL, Charlton B, Leadbetter J, Guasconi A, Aitken ML. Efficacy and safety of inhaled dry-powder mannitol in adults with cystic fibrosis: An international, randomized controlled study. J Cyst Fibros. 2021 Nov;20(6):1003-1009. doi: 10.1016/j.jcf.2021.02.011. Epub 2021 Mar 11.

Reference Type: DERIVED

PMID: 33715994 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DPM-CF-303

Identifier Type: -

Identifier Source: org_study_id