Overview

Whole Lung Lavage (WLL)/Inhaled Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (PAP)

Status:
Unknown status

Trial end date:
2013-07-01

Target enrollment:
0

Participant gender:
All

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).

Phase:

Phase 2/Phase 3

Accepts Healthy Volunteers?

Details

Lead Sponsor:

IRCCS Policlinico S. Matteo

Collaborator:

Agenzia Italiana del Farmaco

Treatments:

Molgramostim
Sargramostim

Criteria

Inclusion Criteria:

- First step: only autoimmune PAP subjects will be included

- Second step (eligibility for the WLL):

- presence of persistent or progressive respiratory failure (PaO2 at rest < 60 mm
Hg)

- absence of respiratory failure at rest, but evidence for exertional

- desaturation < 90% or > 5 percentage points using the modified Bruce's protocol
(5)

- careful evaluation of conditions contraindicating the WLL (see below)

- discussion with the patient about cost-effectiveness of the procedure and
signature of the standard informed consent. Points a) and b) will be evaluated
over a period of 3 months, to avoid spontaneous improvement or resolution.

(The former happens in 10% of cases falling in point b): in the case of fluctuation of
saturation values around the threshold value, the procedure will be delayed until values
are stable; the latter happened in 2/51 autoimmune PAP patients from our series, and the
complete resolution occurred within the first 2 months from the diagnosis.)

- Third step (eligibility for the study): this step will be accomplished essentially by
evaluation of the presence of conditions contraindicating the GM-CSF inhalation and
upon ad hoc informed consent obtained from the patient

Exclusion Criteria:

- chronic lung disease associated with already existing respiratory failure (such as
pulmonary emphysema or fibrosis)

- chronic heart failure or ischemic heart disease

- active pulmonary embolism

- progressive cancer

- other severe metabolic conditions

- secondary PAP

- previously experience of severe and unexplained side-effects during aerosol delivery
of any kinds of agents