Resumen

Este ensayo clínico tiene como objetivo proporcionar evidencia prospectiva de la seguridad y eficacia de manitol 400 mg b.i.d. en sujetos de 18 años de edad o mayores. Se plantea la hipótesis de que manitol inhalado 400 mg b.i.d. aumentará el cambio medio desde el valor basal del FEV1 (mL) en comparación con el control durante el período de tratamiento de 26 semanas en sujetos adultos con fibrosis quística. Cualquier mejoría en el FEV1 se considera clínicamente significativa; sin embargo, este ensayo clínico ha establecido un umbral de 80 mL con el fin de determinar un tamaño de muestra adecuado para la potencia estadística, manteniendo al mismo tiempo la viabilidad del ensayo en una población con enfermedad huérfana.

Descripción detallada

Este es un ensayo clínico doble ciego, aleatorizado, de brazos paralelos, controlado, multicéntrico e intervencionista. Los posibles sujetos firmarán el formulario de consentimiento informado (ICF) y se evaluará su elegibilidad. Tras cumplir todos los criterios de inclusión y exclusión, los sujetos recibirán una prueba de tolerancia al manitol (MTT). Aquellos sujetos que aprueben la MTT serán aleatorizados para recibir manitol inhalado (400 mg b.i.d.) o control b.i.d. durante un período de 26 semanas.

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