A Safety and Efficacy Trial of Inhaled Mannitol in Adult Cystic Fibrosis Subjects
- Registration Number
- NCT02134353
- Lead Sponsor
- Syntara
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 423
- Have given written informed consent to participate in this trial 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 at least 18 years old;
- Have FEV1 > 40 % and < 90% predicted (using NHanes III [1]);
- Be able to perform all the techniques necessary to measure lung function;
- 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
- 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
- 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;
- Be considered "terminally ill" or eligible for lung transplantation;
- Have had a lung transplant;
- Be using maintenance nebulized hypertonic saline in the 2 weeks prior to visit 1;
- Have had a significant episode of hemoptysis (> 60 mL) in the three months prior to Visit 0;
- Have had a myocardial infarction in the three months prior to Visit 0;
- Have had a cerebral vascular accident in the three months prior to Visit 0;
- Have had major ocular surgery in the three months prior to Visit 0;
- Have had major abdominal, chest or brain surgery in the three months prior to Visit 0;
- Have a known cerebral, aortic or abdominal aneurysm;
- Be breast feeding or pregnant, or plan to become pregnant while in the trial;
- Be using an unreliable form of contraception (female subjects at risk of pregnancy only);
- Be participating in another investigative drug trial, parallel to, or within 4 weeks of screening (Visit 0);
- Have a known allergy to mannitol;
- Be using non-selective oral beta blockers;
- Have uncontrolled hypertension -i.e. 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 subject's participation in the trial;or
- Have a failed or incomplete MTT at trial entry (as evaluated in Section 8.1.1.1).
- The subject must not commence treatment with rhDNase or maintenance antibiotics during the trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental arm A Inhaled mannitol Active treatment. Inhaled Mannitol
- Primary Outcome Measures
Name Time Method Mean Change in FEV1 (mL) From Baseline (Visit 1) Over the 26-week Treatment Period (to Visit 4). 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.
Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline FVC (mL) Over the 26-week Treatment Period 26 weeks To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control for improving lung function as measured by mean change from baseline forced vital capacity (FVC) (mL) over the 26-week treatment period in adult subjects with cystic fibrosis (CF).
The mean absolute change from baseline FVC (mL) over 26 weeks 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 change from baseline averaged over the treatment period (ie the average of the changes at 6 weeks, 14 weeks and 26 weeks).
Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).
Trial Locations
- Locations (100)
Cystic Fibrosis Center of Chicago
🇺🇸Glenview, Illinois, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Washington
🇺🇸Seattle, Washington, United States
Hospital del Tórax Cetrángolo
🇦🇷Buenos Aires, Argentina
Hospital Regional Español de Bahía Blanca
🇦🇷Buenos Aires, Argentina
Hospital San Roque
🇦🇷Cordoba, Argentina
UZ Leuven
🇧🇪Leuven, Belgium
Pediatrics Pulmonary Department Rambam Healthcare Campus
🇮🇱Haifa, Israel
Schneider Children's Medical Center of Israel
🇮🇱Petah-Tikva, Israel
CEPREP- Hospital Universitario
🇲🇽Monterrey, Mexico
Detská fakultná nemocnica Košice
🇸🇰Košice, Slovakia
University of Miami
🇺🇸Miami, Florida, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Dr Lawrence Sinde
🇺🇸Mobile, Alabama, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Central Florida Pulmonary Group, P.A.
🇺🇸Orlando, Florida, United States
Illinois Lung Institute
🇺🇸Peoria, Illinois, United States
CHR Citadelle
🇧🇪Liege, Belgium
QEII Health Sciences Center
🇨🇦Halifax, Canada
Mosdós Tüdőgyógyintézet
🇭🇺Mosdós, Hungary
Podkarpacki Osrodek Pulmonologii i Alergologii
🇵🇱Rzeszow, Poland
Kremenchuk First City Hospital n.a. O.T.Bogaevskyy
🇺🇦Kremenchuk, Ukraine
Dnipropetrovsk State Medical Academy, Faculty Theraphy and Endocrinology Chair
🇺🇦Dnipropetrovsk, Ukraine
University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
University of Cape Town Lung Institute
🇿🇦Cape Town, South Africa
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Pediatric Pulmonology
🇺🇸Long Beach, California, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Dr Mitchell Rothstein
🇺🇸Jacksonville, Florida, United States
Dr Joseph Ojile
🇺🇸Saint Louis, Missouri, United States
Spectrum Health Offices of Research Administration
🇺🇸Grand Rapids, Michigan, United States
Dr Allen Dozor
🇺🇸Valhalla, New York, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Dartmouth-Hitchcock Specialty Care
🇺🇸Bedford, New Hampshire, United States
Kosair Charities Pediatric Clinical Research Unit
🇺🇸Louisville, Kentucky, United States
UZ VUB
🇧🇪Brussels, Belgium
Unidad Médica de Occidente
🇲🇽Guadalajara, Mexico
Arke Estudios Clinicos S.A
🇲🇽Mexico City, Mexico
FN Brno
🇨🇿Brno, Czechia
John Hopkins
🇺🇸Baltimore, Maryland, United States
Spedali Civili Brescia
🇮🇹Brescia, Italy
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
St. Augustine's Medical Centre 2
🇿🇦Durban, South Africa
The Toledo Hospital and Toledo Childrens Hospital
🇺🇸Toledo, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
One Richland Medical Park
🇺🇸Columbia, South Carolina, United States
Medical University of SC
🇺🇸Charleston, South Carolina, United States
The Cystic Fibrosis Center Beth Israel Medical Center
🇺🇸New York, New York, United States
Hospital Interzonal General de Agudos Dr. Jose Penna
🇦🇷Bahia Blanca, Argentina
Cystic Fibrosis Center Hospital San Carlo
🇮🇹Potenza, Italy
Azienda Ospedaliera Universitaria Integratadi Verona
🇮🇹Verona, Italy
Országos Korányi Tbc
🇭🇺Budapest, Hungary
Wojewodzki Specjalistyczny Szpital Dzieciecy im. W. Buszkowskiego
🇵🇱Kielce, Poland
Mikhail Smirnov
🇷🇺Vladimir, Russian Federation
Clinical Hospital# 2
🇷🇺Yaroslavl, Russian Federation
Institut de recherches cliniques de Montréal
🇨🇦Montréal, Canada
The Ottawa Hospital, General Campus
🇨🇦Ottawa, Canada
Klinikai Farmakológiai Központ
🇭🇺Debrecen, Hungary
IRCCS Ca' Granda Ospedale Maggiore Policlinico Mil
🇮🇹Milano, Italy
Centro Fibrosi Cistica Policlinico Umberto I
🇮🇹Roma, Italy
AOU San Luigi Gonzaga
🇮🇹Orbassano, Italy
Aziendao Spedaliera Universitaria
🇮🇹Parma, Italy
Törökbálint Tüdőgyógyintézet
🇭🇺Törökbálint, Hungary
Instituto Jaliscience de Investigacion Clinica
🇲🇽Guadalajara, Mexico
Institutul de Pneumoftiziologie "Marius Nasta" Bucuresti, Sectia Clinica Pneumologie V
🇷🇴Bucuresti, Romania
Spitalul Clinic de Pneumoftiziologie Lasi
🇷🇴Lasi, Romania
Oddelenie pneumológie a ftizeológie
🇸🇰Banská Bystrica, Slovakia
Imuno-alergologická ambulancia
🇸🇰Bratislava, Slovakia
Hospital Virgen del Rocio Hospital Unidad de Fibrosis Quistica
🇪🇸Sevilla, Spain
Research and Clinical Center of interstitial and orphan lung diseases
🇷🇺Saint-Petersburg, Russian Federation
Hospital Universitario La Fe Neumología
🇪🇸Valencia, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Spain
Municipal Institution "Kherson City Clinical Hospital n.a. Afanasiy and Olha Tropin
🇺🇦Kherson, Ukraine
Hospital Universitaro La Paz
🇪🇸Madrid, Spain
Tampa General Hospital
🇺🇸Tampa, Florida, 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
Mater Adult Hospital
🇦🇺Brisbane, Queensland, Australia
Greenlane Hospital
🇳🇿Auckland, New Zealand
Canterbury Respiratory Research Group
🇳🇿Christchurch, New Zealand
Otago Respiratory Research Unit, Dunedin Hospital
🇳🇿Dunedin, New Zealand
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
University of CA, Davis
🇺🇸Sacramento, California, United States
The Children's Medical Center of Dayton
🇺🇸Dayton, Ohio, United States
Insares
🇦🇷Mendoza, Provincia De Mendoza, Argentina
Szpital Dziecięcy Polanki im. M. Płażyńskiego w Gdańsku sp.
🇵🇱Gdańsk, Poland
Centrum Medyczne Karpacz SA
🇵🇱Karpacz, Poland
Wojewodzki Szpital Specjalistyczny im.
🇵🇱Lodz, Poland
Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
🇵🇱Poznan, Poland
Sanatorium Cassia-Villa Medica S.C.
🇵🇱Rabka Zdroj, Poland
Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"
🇷🇴Bucuresti, Romania
Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca
🇷🇴Cluj - Napoca, Romania
Tatiana I. Martynenko
🇷🇺Barnaul, Russian Federation
Pulmonology Research Institute
🇷🇺Moscow, Russian Federation
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