Clinical Trial: Whole Lung Lavage (WLL)/Inhaled Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (PAP)
Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional
Official Title: Whole Lung Lavage Followed by Inhaled Sargramostim in the Treatment of Autoimmune Pulmonary Alveolar Proteinosis
Brief Summary: The investigators designed an experimental, randomized by parallel groups, stratified according to previous treatment, open-label study evaluating the superiority of the combination of whole lung lavage/inhaled GM-CSF versus whole lung lavage alone in patients with pulmonary alveolar proteinosis. The primary efficacy objective is the total resolution of the pulmonary involvement. PAP patients matching the enrolment criteria will enter the study. If requiring the first WLL, they will be randomized to receive WLL (1st level control group) or WLL/followed by inhaled GM-CSF, according to an acute (12 weeks) followed by maintenance (6 months) schedule (1st level treated group).
Detailed Summary:
Background:
Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by accumulation of lipoproteinaceous material within alveolar spaces, leading to respiratory failure. Whole lung lavage (WLL) is the current therapeutic option, but it may induce complete resolution of the disorder only in 30% of patients. Based on PAP pathophysiology, a few pilot studies dealing with administration of rGM-CSF (Sargramostim) to patients either s.c. or aerosolized have been performed, with hopeful results.Objectives. We designed an experimental, randomized by parallel groups, stratified according to previous treatment, open-label study looking at evaluation the superiority of the combination WLL/inhaled GM-CSF vs WLL alone in PAP patients. The study also includes a side, observational section. The primary efficacy objective is the total resolution of the pulmonary involvement in all treated patients. The study includes some secondary efficacy objectives as well: avoidance of disease recurrence, avoidance of respiratory infections, investigation of biomarkers predicting the disease outcome, effect of treatments on underlying pathophysiology of PAP.
Methods:
PAP patients matching the enrollment criteria will enter the study. 1) If requiring the first WLL, they will be randomized to receive WLL (1st level control group) or WLL/ followed by inhaled GM-CSF, according to an acute (12 weeks) followed by maintenance (6 months) schedule (1st level treated group). 2) PAP patients requiring the second WLL: a) the 1st level control group subjects will be randomized to receive WLL alone (2nd level control group) or WLL/GM-CSF (2nd level treated group); b) the 1st level treated group will receive WLL/GM-CSF (1st level re-treated group). 3) PAP patients requiring the 3rd WLL will receive WLL/
Sponsor: IRCCS Policlinico S. Matteo
Current Primary Outcome: The total resolution of the pulmonary involvement [ Time Frame: 36 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Avoidance of recurrence of the disease requiring multiple WLLs [ Time Frame: 36 months ]
- Investigation of determinants of the outcome [ Time Frame: 36 months ]
Original Secondary Outcome: Same as current
Information By: IRCCS Policlinico S. Matteo
Dates:
Date Received: May 11, 2009
Date Started: July 2009
Date Completion: July 2013
Last Updated: July 27, 2009
Last Verified: July 2009
