Establishment of a FeNO Cutoff Value for Evaluating the Response to Budesonide-formoterol in Patients With Chronic Cough Suggestive of Cough Variant Asthma: a Multicenter Prospective Clinical Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- To obtain a cut-off value for FeNO which can be used to distinguish responsiveness to 8 weeks treatment of Budesonideformoterol (based on visual analog scale [VAS]).
研究概览
简要总结
This is a multicenter, prospective, single-arm, interventional clinical study to predict the response to budesonide-formoterol treatment in patients with chronic dry or nocturnal cough by determining a cut off value of FeNO. In this study, the response to ICS/LABA treatment is defined as reduction in cough VAS score from baseline of ≥30 mm after 8 weeks of ICS/LABA treatment. Subjects will be treated with Symbicort® 160/4.5 mcg, 1 puff, BID for 8 weeks with 4 study visits: Visit 1 (Day 0), Visit 2 (week 4) and Visit 3, end of study (week 8) and Visit 4, 4 weeks after treatment discontinuation, (week 12). Baseline data will be collected at Day-5 to Day0.
This study will be conducted at around 40 study sites in China. Approximately 1000 patients (age ≥18 years old) with dry cough or nocturnal cough symptoms for at least 8 weeks and no other obvious cause for their cough will be enrolled into this study.
详细描述
This is a multicenter, prospective, single-arm, interventional clinical study to predict the response to budesonide-formoterol treatment in patients with chronic dry or nocturnal cough by determining a cut off value of FeNO. In this study, the response to ICS/LABA treatment is defined as reduction in cough VAS score from baseline of ≥30 mm after 8 weeks of ICS/LABA treatment. Subjects will be treated with Symbicort® 160/4.5 mcg, 1 puff, BID for 8 weeks with 4 study visits: Visit 1 (Day 0), Visit 2 (week 4) and Visit 3, end of study (week 8) and Visit 4, 4 weeks after treatment discontinuation, (week 12). Baseline data will be collected at Day-5 to Day0.
This study will be conducted at around 40 study sites in China. Approximately 1000 patients (age ≥18 years old) with dry cough or nocturnal cough symptoms for at least 8 weeks and no other obvious cause for their cough will be enrolled into this study. Disclosure Statement: This is an Interventional study with single arm.
Number of Participants:
Approximately 1150 participants will be screened to achieve 1000, based on assuming a screen failure rate of approximately 15%. assigned to study intervention. Study Arms and Duration: Single-arm, 2 months Data Monitoring / Other Committee: Not applicable Statistical Methods： In general, descriptive statistics will be provided for the data collected. For continuous variables, mean, standard deviation, median, quartiles, minimum and maximum will be provided, and for categorical variables, frequency counts and percentages for each category will be provided. Missing data will not be imputed unless otherwise specified. The diagnostic value of FeNO to Budesonide-formoterol response will be measured as the area under the curve (AUC) of the receiver-operating characteristic derived from the Logistic regression model. The study is mainly to investigate if FeNO alone can help to distinguish patients with Budesonide-formoterol response or not, and therefore baseline FeNO value will be the only independent variable included in the model. The optimal cutoff value will be selected by consulting clinical experts, and based on comprehensive assessment of AUC, sensitivity, specificity, PPV, and NPV of different FeNO cut points. To perform discovery and validation within the same study, the total sample will be split randomly into discovery and validation datasets by 70% and 30% respectively. For the validation, similar parameters of diagnostic values will be calculated and compared with those based on the discovery dataset.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Subjects who voluntarily participate in the study and comply with the study requirements, understand, comply with and cooperate with the corresponding examinations, comply with the follow-up schedule, and voluntarily sign the written informed consent form.
- •Patients aged ≥ 18 years.
- •Subjects with cough as the predominant or sole symptom, and manifested as dry or nocturnal cough lasting for ≥ 8 weeks.
- •FEV1/FVC ≥ 70% within 4 weeks from the enrolment.
- •No clinically significant abnormality in the chest CT within 3 months from the enrolment.
- •Cough VAS score ≥ 40 mm measured within 48 hours before enrollment.
排除标准
- •Any history of respiratory infection within 8 weeks from the enrolment.
- •Dyspnea caused by respiratory system disorders.
- •Patients with GERC, upper airway cough syndrome/postnasal drip syndrome as the likely cause of cough.
- •Patients with suspected AECI induced cough.
- •Intolerance to β2 agonists.
- •Used ICS-containing drugs within 8 weeks before enrollment, including ICS or ICS/LABA and so on.
- •Used oral corticosteroids within 8 weeks before enrollment.
- •Used LTRA within 8 weeks before enrollment.
- •Current smokers, or former smokers with a smoking cessation interval of less than 6 months; Smokers with a pack history of greater than 20 pack-years.
- •Individuals with severe respiratory or other systemic diseases.
- •Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator.
研究组 & 干预措施
Budesonide-Formoterol treatment
Budesonide 160 μg/formoterol 4.5 μg, 1 inhalation, BID
干预措施: Budesonide-Formoterol treatment (Drug)
结局指标
主要结局
To obtain a cut-off value for FeNO which can be used to distinguish responsiveness to 8 weeks treatment of Budesonideformoterol (based on visual analog scale [VAS]).
时间窗: 8 weeks
Area under the ROC Curve (AUC), sensitivity, specificity, PPV, NPV
次要结局
- To obtain a cut-off value for FeNO which can be used to distinguish responsiveness to 8 weeks treatment of Budesonideformoterol (based on leicester cough questionnaire [LCQ]).(8 weeks)
- To obtain a cut-off value for FeNO which can be used to distinguish responsiveness to 8 weeks treatment of Budesonideformoterol (based on cough evaluation test [CET]).(8 weeks)
- To assess if the 8 weeks treatment of Budesonide-formoterol response rate differ between the high FeNO group and low FeNO group using the identified cut-off value(8 weeks)