A Prospective Study of Inhaling Granulocyte-macrophage Colony Stimulating Factor in Adult Patients With Mild-to-moderate Autoimmune Pulmonary Alveolar Proteinosis in China: a Randomized Open-label Study
试验速览
- 阶段
- 2 期
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- A-aDO2 difference
研究概览
简要总结
The purpose of the study is to evaluate if inhaled granulocyte-macrophage colony stimulating factor delay the increase in alveolar-arterial oxygen difference, compared to no treatment, for adult patients with mild-to-moderate autoimmune pulmonary alveolar proteinosis in China over a two-year period.
详细描述
Autoimmune pulmonary alveolar proteinosis (PAP, previously known as idiopathic PAP) is a rare interstitial lung disease elicited by the formation of autoantibodies which neutralize the activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) which decreases macrophage clearance of surfactant.
Currently, the standard treatment strategy for PAP is whole lung lavage (WLL)，which is invasive and has limitations. Inhaled GM-CSF therapy became a new option for PAP patients not only because of its effectiveness and safety, but it is convenient way for patients who are reluctant to do operation as well. We are planning to prospectively evaluate if inhaled granulocyte-macrophage colony stimulating factor would delay the increase in alveolar-arterial oxygen difference (A-aDO2, which is the most sensitive factor in evaluating APAP5), compared to placebo, for patients with mild-to-moderate autoimmune pulmonary alveolar over a two-year period.
A total of 42 subjects with APAP who meet the inclusion criteria will be enrolled at Peking Union Medical College Hospital and Nanjing Drum Tower Hospital. After observe APAP patients for 3 months to rule out patients who resolved spontaneously, the participants will undergo randomization (by random number table)and stratified into two different groups by their DSS. Then they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week or no treatment for 6 months, and will be followed on an outpatient basis at 2 weeks, and 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after initiation of therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult autoimmune PAP subjects will be included: 1) a positive PAS stain from BALF or lung biopsy; 2) high level of serum anti-GM-CSF antibody (>2.39ug/ml, the cut-off point in our hospital); 3) age above 18 years old; 4) exclude hereditary and secondary PAP.
- •Able to give written informed consent and comply with the requirements of the study.
- •Patients are not eligible for the whole lung lavage (WLL), decided by clinicians.
- •Eligibility for GM-CSF inhalation: 1) Disease severity score (DSS) is 1-3; 2) No treatment with GM-CSF therapy or WLLin the 3 months prior to enrollment. Definition of DSS2: 1, no symptom and PaO2>=70mmHg；2, PaO2>=70mmHg with symptoms；3, PaO2>=60 and <70mmHg; 4, PaO2>=50 and <60mmHg; 5, PaO2<50mmHg.
排除标准
- •Patients will be observed for 3 months and all APAP patients who resolved spontaneously will be excluded from our study.
- •PAP resulting from another condition (e.g. occupational exposure to silica, underlying HIV, respiratory infections, myeloproliferative disorder or leukaemia);
- •A normal or low-titre serum anti-GM-CSF antibody (≤2.39ug/ml);
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies；
- •Chronic lung disease associated with already existing respiratory failure (such as pulmonary emphysema or fibrosis);
- •Other serious medical conditions which, in the opinion of the investigator, would make the patient unsuitable for the study.
- •Pregnancy.
研究组 & 干预措施
GM-CSF, nebulizer
After the patients were randomly divided into two groups, they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week for 6 months.
干预措施: GM-CSF (Drug)
结局指标
主要结局
A-aDO2 difference
时间窗: 2 years
次要结局
- Time to relapse(up to 2 years)
- Severe adverse event(2 years)
- 6 minutes walking distance difference(2 years)
- FEV1 difference(2 years)
研究者
Kaifeng Xu
MD
Peking Union Medical College Hospital