Azithromycin Treatment for Non-eosinophilic Chest Tightness Variant Asthma

NCT ID: NCT05596721

Last Updated: 2022-11-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 248 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2024-03-31

Brief Summary

Bronchial asthma (abbr. asthma) is one of common airway chronic inflammatory disease which usually threatens human health. Typical symptoms of asthma are recurrent wheezing, shortness of breath, chest tightness and cough, usually happened at night or in early morning. However, there are still some patients who persist only clinical manifestations of chest tightness, namely, chest tightness variant asthma (CTVA). This subgroup of asthma usually lacks asthma-specific clinical features, therefore, often misdiagnosed and lack of effective treatment for a long time. The investigators' previous studies have found that CTVA has eosinophilic and non-eosinophilic subtypes. These patients with non-eosinophilic CTVA (NE-CTVA) are not sensitive to ICS/LABA, which guidelines recommend. At present, the specific treatment plan for NE-CTVA is urgently needed to elucidate. Azithromycin has immunomodulatory and anti-inflammatory effects in addition to their antibacterial effects. Maintenance treatment with azithromycin has been proved to be effective in chronic neutrophilic airway diseases and severe asthma. However, there are no clinical studies to confirm the effectiveness of azithromycin in non-eosinophilic asthma, especially atypical asthma such as NE-CTVA. Now the investigators performed a national multi-center study to explore whether azithromycin improves asthma symptom control and improves quality of life in people with NE-CTVA. Finally, to find an optimal treatment for NE-CTVA.

Detailed Description

Bronchial asthma (abbr. asthma) is one of common airway chronic inflammatory disease which usually threatens human health. Typical symptoms of asthma are recurrent wheezing, shortness of breath, chest tightness and cough, usually happened at night or in early morning. However, there are still some patients who persist only clinical manifestations of chest tightness. Focus on this group of patients, the investigators proposed a subgroup of bronchial asthma, namely, chest tightness variant asthma (CTVA). This subgroup of asthma usually lacks asthma-specific clinical features such as wheezing, shortness of breath, wheezing, therefore, often misdiagnosed for a long time.

The investigators' previous studies have found that CTVA is like the clinical classification of common asthma and cough variant asthma (CVA), and there are also eosinophilic and non-eosinophilic subtypes in CTVA. These patients with non-eosinophilic CTVA (NE-CTVA) are not sensitive to ICS/LABA, which guidelines recommend, and have lower FeNO values than sensitive CTVAs. At present, the specific treatment plan for NE-CTVA is a special clinical asthma phenotype, and further clinical studies are urgently needed to elucidate.

Azithromycin has immunomodulatory and anti-inflammatory effects in addition to their antibacterial effects. Maintenance treatment with azithromycin has been proved to be effective in chronic neutrophilic airway diseases including chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis and diffuse panbronchiolitis. Whilst azithromycin is effective and recommended in current American Thoracic Society (ATS) / European Respiratory Society (ERS) and Global Initiative for Asthma (GINA) guidelines for selected persistently symptomatic adults with severe asthma. However, there are no clinical studies to confirm the effectiveness of azithromycin in non-eosinophilic asthma, especially atypical asthma such as NE-CTVA.

The investigators conduct a national multi-center, prospective randomized trial to test the hypothesis that azithromycin improves symptom control and improves quality of life in people with NE-CTVA. To this end, the recruited participants will be randomly divided into ICS/LABA + azithromycin group and ICS/LABA group. The treatment period is 12 weeks, and then to evaluate the revised-asthma control questionnaire (r-ACQ) score, asthma quality of life questionnaire (AQLQ) score, self-rating anxiety scale (SAS), self-rating depression scale (SDS), lung function, and numbers of emergency or hospitalization. Provide clinical evidence for the optimal treatment of NE-CTVA.

Conditions

Asthma; Chest Syndrome; Azithromycin; Effect of Drug

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azithromycin + ICS/LABA

Azithromycin: 500mg, po, 3 times per week for 12w ICS/LABA: Budesonide and Formoterol Fum arate Powder for Inhalation, 1 inhale, bid for 12w

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Treat patient with azithromycin for 12w.

ICS/LABA

Intervention Type: DRUG

Treat patient with ICS/LABA according to Global Initiative for Asthma (GINA) guideline.

ICS/LABA

ICS/LABA: Budesonide and Formoterol Fum arate Powder for Inhalation, 1 inhale, bid for 12w

Group Type: PLACEBO_COMPARATOR

ICS/LABA

Intervention Type: DRUG

Treat patient with ICS/LABA according to Global Initiative for Asthma (GINA) guideline.

Interventions

Azithromycin

Treat patient with azithromycin for 12w.

Intervention Type: DRUG

ICS/LABA

Treat patient with ICS/LABA according to Global Initiative for Asthma (GINA) guideline.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. all subjects agreed to participate, understand the project, observe the use of drugs, agree to follow-up, and signed informed consent;

2. the age of more than 14 and less 80 years old, gender and ethnicity are not limited;

3. the duration time was more than 6 months,and chest tightness was the only complaint, without breathing, short of breath, chronic cough;

4. no wheezing;

5. a diagnosis of asthma supported by one or more other characteristics:

• bronchial provocation test positive;
• improvement in forced expiratory volume at one second (FEV1) of more than 12% and 200 ml after inhaled salbutamol;
• variability in diurnal peak expiratory flow (PEF) of more than 10% for one day during one week.

6. blood eosinophils < 150/µl and FeNO < 20 ppb;

7. exclude the following diseases by the corresponding doctors: coronary heart disease, myocarditis, heart failure, GERD, neuromuscular disease, and mental disease.

Exclusion Criteria

1. can not cooperate with related inspection or for other reasons;

2. patients with chronic obstructive pulmonary disease, interstitial pneumonia, active tuberculosis, community acquired pneumonia, lung cancer, bronchiectasis, cor pulmonale, pulmonary embolism, and accompanied with serious systematic disease (such as coronary heart disease, myocarditis, heart failure, gastroesophageal reflux disease, neuromuscular disease, etc);

3. history of chronic hepatic kidney or neurologic disorder;

4. history of drug abuse, alcohol abuse or anesthesia or with a history of mental illness (schizophrenia, obsessive-compulsive disorder, depression) and against personality, motivation, suspicious, or other emotional or mental issues that may affect participation in the study;

5. taking part in other drug clinical trial project, or drop out less than 3 months;

6. during pregnancy, lactation women;

7. obvious abnormal of High Resolution CT;

8. macrolide allergy;

9. received azithromycin treatment in the past 2 weeks;

10. hearing impairment or abnormally prolonged QTc interval.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huahao Shen, M.D.

Role: STUDY_CHAIR

The Second Affiliated Hospital, School of Medicine, Zhejiang University, China

Locations

China-Japan Friendship Hospital

Beijing, Beijing Municipality, China

Xinqiao Hospital, Third Military Medical University

Chongqing, Chongqing Municipality, China

The First Affiliated Hospital,Guangzhou Medical University

Guangzhou, Guangdong, China

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Jiangsu Province Hospital

Nanjing, Jiangsu, China

The Central Hospital of Shenyang Military

Shenyang, Liaoning, China

Xijing Hospital

Xi'an, Shaanxi, China

Qilu Hospital, Shandong University

Jinan, Shandong, China

Changhai Hospital, Second Military Medical University

Shanghai, Shanghai Municipality, China

Ruijin Hospital, Shanghai Jiaotong University

Shanghai, Shanghai Municipality, China

Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

The Second Affiliated Hospital, School of Medicine, Zhejiang University, China

Hanzhou, Zhejiang, China

Countries

China

Central Contacts

Wen Hua, M.D.

Role: CONTACT

hw1983@126.com

+86 0571 87783552

Facility Contacts

Nan Su, M.D.

Role: primary

Changzheng Wang, M.D.

Role: primary

Nanshan Zhong, M.D.

Role: primary

Xudong Xiang, M.D.

Role: primary

Mao Huang, M.D.

Role: primary

Hua Xie, M.D.

Role: primary

Changgui Wu, M.D.

Role: primary

Yan Shang, M.D.

Role: primary

Huanying Wan, M.D.

Role: primary

Xin Zhou, M.D.

Role: primary

Wen Hua, M.D.

Role: primary

Other Identifiers

AZNECTVA

Identifier Type: -

Identifier Source: org_study_id