Azithromycin Treatment for Non-eosinophilic Chest Tightness Variant Asthma

Phase 4

Not yet recruiting

• Conditions: Asthma; Effect of Drug; Chest Syndrome; Azithromycin
• Interventions: Drug: ICS/LABA; Drug: Azithromycin

• Registration Number: NCT05596721
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

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.

Study Timeline

• Status Verified: 2022-10
• Study First Submitted: 2022-10-25
• Study First Submitted QC: 2022-10-26
• Study First Posted: 2022-10-27
• Last Update Submitted: 2022-11-02
• Last Update Posted: 2022-11-04
• Study Start: 2023-01-01
• Primary Completion: 2024-03-31
• Study Completion: 2024-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 248

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
r-ACQ	Change from Baseline ACQ at 12 weeks	Revised-asthma control questionnaire.

Secondary Outcome Measures

Name	Time	Method
FEV1	Change from Baseline at 4 weeks, 8 weeks, and 12 weeks	Perform pulmonary function tests of patients and record the forced expiratory volume in one second.
Airway responsiveness	Change from Baseline at 4 weeks, 8 weeks, and 12 weeks	Perform pulmonary function tests of patients and record the PD20-FEV1.
SAS	Change from Baseline at 4 weeks, 8 weeks, and 12 weeks	Self-rating Anxiety Scale.
PEF	Change from Baseline at 4 weeks, 8 weeks, and 12 weeks	Perform pulmonary function tests of patients and record the peak expiratory flow.
SDS	Change from Baseline at 4 weeks, 8 weeks, and 12 weeks	Self-rating Depression Scale.
AQLQ	Change from Baseline at 4 weeks, 8 weeks, and 12 weeks	Asthma quality of life questionnaire.
Numbers of emergency or hospitalization	Change from Baseline at 4 weeks, 8 weeks, and 12 weeks	Record the numbers of emergency or hospitalization because asthma.

Trial Locations

Locations (13)

The First Affiliated Hospital,Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China

The Second Xiangya Hospital of Central South University; 🇨🇳 Changsha, Hunan, China

Qilu Hospital, Shandong University; 🇨🇳 Jinan, Shandong, China

Ruijin Hospital, Shanghai Jiaotong University; 🇨🇳 Shanghai, Shanghai, China

Xinqiao Hospital, Third Military Medical University; 🇨🇳 Chongqing, Chongqing, China

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China

Jiangsu Province Hospital; 🇨🇳 Nanjing, Jiangsu, China

The Central Hospital of Shenyang Military; 🇨🇳 Shenyang, Liaoning, China

Xijing Hospital; 🇨🇳 Xi'an, Shaanxi, China

Changhai Hospital, Second Military Medical University; 🇨🇳 Shanghai, Shanghai, China

The Second Affiliated Hospital, School of Medicine, Zhejiang University, China; 🇨🇳 Hanzhou, Zhejiang, China

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China

Shanghai General Hospital; 🇨🇳 Shanghai, Shanghai, China