Sequential Therapy With WLL/Inhaling GM-CSF for Autoimmune Pulmonary Alveolar Proteinosis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effectiveness of the sequential therapy with whole lung Lavage (WLL)/inhaling granulocyte-macrophage colony stimulating factor, compared to WLL only, for adult patients with severe autoimmune pulmonary alveolar proteinosis in China over a two-year period.

Official Title
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A Multicenter Clinical Study of the Sequential Therapy With Whole Lung Lavage/Inhaling Granulocyte-macrophage Colony Stimulating Factor in Adult Patients With Severe Autoimmune Pulmonary Alveolar Proteinosis in China

Conditions
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Pulmonary Alveolar Proteinosis, Treatment

Intervention / Treatment
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* Drug: GM-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Comfirmed diagnosis of autoimmune pulmonary alveolar proteinosis Disease severity score (DSS) is 4-5 Exclusion Criteria: The acute respiratory infection Heart failure (such as cardiogenic pulmonary edema) The serious liver and kidney dysfunction (creatinine or ALT were equal to or more than 2 times of the upper limit of normal range); Pregnancy; The patients with hereditary and secondary factors (inhalation of dust, hematological diseases, autoimmune diseases, etc.); DSS is 1-3; The patient is allergic to the drugs that be used in our research; The patients with poor compliance, or suffering from mental illness; The patients have not signed informed consent; They were treated with whole lung lavage or regular GM-CSF therapy (treatment for more than 2 weeks) within 3 months before the enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GM-CSF<br>After the patients were randomly divided into two groups, they will receive whole lung lavage (WLL), and then one of the two groups with continue the next step as follows: Induction period: The time of beginning is 1 week after whole lung lavage, aerosolized GM-CSF was given for 7 days (150ug bid), and then the durg was stopped for 7 days, the 2 weeks was designed as a cycle, a total of 6 cycles (3 months) were known as the induction period. Maintenance period: maintenance period came up after the induction period. The dose of aerosolized GM-CSF was reduced to 150ug/d for three times a week, and then the durg was stopped for 7 days, the 2 weeks was designed as a cycle and maintenance period lasted for 9 months. | Drug: GM-CSF<br>* After the patients were randomly divided into two groups, they will receive whole lung lavage (WLL), and then one of the two groups with continue the next step as follows: Induction period: The time of beginning is 1 week after whole lung lavage, aerosolized GM-CSF was given for 7 days (150ug bid), and then the durg was stopped for 7 days, the 2 weeks was designed as a cycle, a total of 6 cycles (3 months) were known as the induction period. Maintenance period: maintenance period came up after the induction period. The dose of aerosolized GM-CSF was reduced to 150ug/d for three times a week, and then the durg was stopped for 7 days, the 2 weeks was designed as a cycle and maintenance period lasted for 9 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the first relapse (the date: day/month/year) | The standard of relapse: the condition of the disease after GM-CSF inhalation meeted the standard of effective treatment or the stability criteria, and then the condition deteriorated and meeted the deteriorate standard. The standard of effective treatment: oxygenation improvement (an increase in PaO2 of more than 10mmHg and / or a reduction in A-aDO2 more than 10mmHg). The stability criteria: an increase or a reduction in PaO2 of less than 10mmHg and / a reduction or an increase in A-aDO2 of less than 10mmHg. The deteriorate standard: deteriorate oxygenation (a reduction in PaO2 of more than 10mmHg and / or an increase in A-aDO2 of more than 10mmHg). | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse rate |  | Up to 2 years | 
| FEV1 difference |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary alveolar proteinosis, granulocyte-macrophage colony-stimulating factor, whole lung lavage