Clinical trial NCT06590740: Establish FeNO Cut-off Value for Predicting Budesonide-formoterol Response in Chronic Cough Suggestive of CVA Patients.
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cough-Variant Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Patients aged ≥ 18 years.
3. Subjects with cough as the predominant or sole symptom, and manifested as dry or nocturnal cough lasting for ≥ 8 weeks.
4. FEV1/FVC ≥ 70% within 4 weeks from the enrolment.
5. No clinically significant abnormality in the chest CT within 3 months from the enrolment.
6. Cough VAS score ≥ 40 mm measured within 48 hours before enrollment.

Exclusion Criteria:

1. Any history of respiratory infection within 8 weeks from the enrolment.
2. Dyspnea caused by respiratory system disorders.
3. Patients with GERC, upper airway cough syndrome/postnasal drip syndrome as the likely cause of cough.
4. Patients with suspected AECI induced cough.
5. Intolerance to β2 agonists.
6. Used ICS-containing drugs within 8 weeks before enrollment, including ICS or ICS/LABA and so on.
7. Used oral corticosteroids within 8 weeks before enrollment.
8. Used LTRA within 8 weeks before enrollment.
9. 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.
10. Individuals with severe respiratory or other systemic diseases.
11. Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator.

Primary outcomes:
measure: 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]).
timeFrame: 8 weeks
Secondary outcomes:
measure: 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]).
timeFrame: 8 weeks
measure: 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]).
timeFrame: 8 weeks
measure: 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
timeFrame: 8 weeks
Other outcomes:
measure: To describe patient's characteristic (FeNO) with 8 weeks treatment of Budesonide-formoterol response and those without Budesonideformoterol response.
timeFrame: 8 weeks
measure: To describe patient's characteristic (blood EOS) with 8 weeks treatment of Budesonide-formoterol response and those without Budesonideformoterol response.
timeFrame: 8 weeks
measure: To describe patient's characteristic (Induced Sputum EOS) with 8 weeks treatment of Budesonide-formoterol response and those without Budesonideformoterol response.
timeFrame: 8 weeks
measure: To describe patient's characteristic (IgE) with 8 weeks treatment of Budesonide-formoterol response and those without Budesonideformoterol response.
timeFrame: 8 weeks
measure: To describe patient's characteristic (visual analog scale [VAS]) with 8 weeks treatment of Budesonide-formoterol response and those without Budesonideformoterol response.
timeFrame: 8 weeks
measure: To describe patient's characteristic (leicester cough questionnaire [LCQ]) with 8 weeks treatment of Budesonide-formoterol response and those without Budesonideformoterol response.
timeFrame: 8 weeks
measure: To describe patient's characteristic (cough evaluation test [CET]) with 8 weeks treatment of Budesonide-formoterol response and those without Budesonideformoterol response.
timeFrame: 8 weeks
measure: To assess the diagnostic value of EOS in distinguishing responsiveness to 8 weeks treatment of Budesonide-formoterol and determine the optional cutoff value for EOS.
timeFrame: 8 weeks
measure: To describe response rate of Budesonideformoterol at 4 and 8 weeks.
timeFrame: 4 weeks, 8 weeks
measure: To explore the bronchial provocation test negative conversion rate in patients with positive baseline provocation test who were treated with budesonide-formoterol for 8 weeks.
timeFrame: 8 weeks
Locations:
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Benxi
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Dongguan
country: China
facility: Research Site
city: Fenyang
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guiyang
country: China
facility: Research Site
city: Heifei
country: China
facility: Research Site
city: Heze
country: China
facility: Research Site
city: Hohhot
country: China
facility: Research Site
city: Huizhou
country: China
facility: Research Site
city: Jiaxing
country: China
facility: Research Site
city: Jinhua
country: China
facility: Research Site
city: Liuzhou
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanyang
country: China
facility: Research Site
city: Quanzhou
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shangqiu
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Weifang
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xiangtan
country: China
facility: Research Site
city: Yantai City
country: China
facility: Research Site
city: Zhengzhou City
country: China
facility: Research Site
city: Zunyi
country: China
facility: Research Site
Study officials:
affiliation: The First Affiliated Hospital of Guangzhou Medical University
name: Kefang Lai
role: PRINCIPAL_INVESTIGATOR
References: