Resumen

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

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 99 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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.

Intervenciones

drug

Inhaled mannitol

Inhaled mannitol 400 mg BD for 26 weeks

drug

Placebo Comparator: Arm B - Control

Placebo Comparator: Arm B - Control BD for 26 weeks

Ubicaciones

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