Azithromycin Treatment for Non-eosinophilic Chest Tightness Variant Asthma

November 2, 2022 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

Effect of Azithromycin With ICS/LABA in Non-eosinophilic Chest Tightness Variant Asthma: a Multicentre Randomized Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

248

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Wen Hua, M.D.
  • Phone Number: +86 0571 87783552
  • Email: hw1983@126.com

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • China-Japan Friendship Hospital
        • Contact:
          • Nan Su, M.D.
    • Chongqing
      • Chongqing, Chongqing, China
        • XinQiao Hospital, Third Military Medical University
        • Contact:
          • Changzheng Wang, M.D.
    • Guangdong
      • Guangzhou, Guangdong, China
        • The First Affiliated Hospital,Guangzhou Medical University
        • Contact:
          • Nanshan Zhong, M.D.
    • Hunan
      • Changsha, Hunan, China
        • The second Xiangya Hospital of Central South University
        • Contact:
          • Xudong Xiang, M.D.
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Jiangsu Province Hospital
        • Contact:
          • Mao Huang, M.D.
    • Liaoning
      • Shenyang, Liaoning, China
        • The Central Hospital of Shenyang Military
        • Contact:
          • Hua Xie, M.D.
    • Shaanxi
      • Xi'an, Shaanxi, China
        • Xijing Hospital
        • Contact:
          • Changgui Wu, M.D.
    • Shandong
      • Jinan, Shandong, China
        • Qilu Hospital, Shandong University
    • Shanghai
      • Shanghai, Shanghai, China
        • Shanghai General Hospital
        • Contact:
          • Xin Zhou, M.D.
      • Shanghai, Shanghai, China
        • Zhongshan Hospital, Fudan University
      • Shanghai, Shanghai, China
        • Changhai Hospital, Second Military Medical University
        • Contact:
          • Yan Shang, M.D.
      • Shanghai, Shanghai, China
        • Ruijin Hospital, Shanghai Jiaotong University
        • Contact:
          • Huanying Wan, M.D.
    • Zhejiang
      • Hanzhou, Zhejiang, China
        • The Second Affiliated Hospital, School of Medicine, Zhejiang University, China
        • Contact:
          • Wen Hua, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 80 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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
Drug: Azithromycin
Treat patient with azithromycin for 12w.
Drug: ICS/LABA
Treat patient with ICS/LABA according to Global Initiative for Asthma (GINA) guideline.
PLACEBO_COMPARATOR: ICS/LABA
ICS/LABA: Budesonide and Formoterol Fum arate Powder for Inhalation, 1 inhale, bid for 12w
Drug: ICS/LABA
Treat patient with ICS/LABA according to Global Initiative for Asthma (GINA) guideline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
r-ACQ
Time Frame: Change from Baseline ACQ at 12 weeks
Revised-asthma control questionnaire.
Change from Baseline ACQ at 12 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Investigators

  • Study Chair: Huahao Shen, M.D., The Second Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

January 1, 2023

Primary Completion (ANTICIPATED)

March 31, 2024

Study Completion (ANTICIPATED)

March 31, 2024

Study Registration Dates

First Submitted

October 25, 2022

First Submitted That Met QC Criteria

October 26, 2022

First Posted (ACTUAL)

October 27, 2022

Study Record Updates

Last Update Posted (ACTUAL)

November 4, 2022

Last Update Submitted That Met QC Criteria

November 2, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AZNECTVA

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe