The Efficacy of Budesonide/Formoterol in Cough Variant Asthma

The Efficacy of Budesonide/Formoterol in Cough Variant Asthma -- A Multi-center Randomized, Controlled Clinical Trial

Cough variant asthma (CVA), subtype of bronchial asthma, is considered to be one of the most common causes of chronic cough in different cough guidelines of United States, Europe, China and other countries. From a multicenter survey in China, over one third of chronic cough is caused by CVA, which is higher than western countries. CVA differs from classic asthma, usually manifesting a symptom of only coughing without wheezing or dyspnea and particularly coughing at night. With less clinical manifestation and medical intervention, CVA patients are easily be neglected and misdiagnosed, and 30-40% of them will develop to typical asthma in the next few years. Currently there's no specific therapy recommendation for CVA in GINA. Although cough guidelines in China recommend that CVA patients should be treated as typical asthma, no recommendation on details about ICS/LABA dosage and duration. There are only a few sporadic CVA therapy researches with small sample size. Two studiesfound that CVA patients can't get cough symptom relief even after treating by low dose of ICS/LABA for 3 months. Some patients' cough symptom relapses during the 24-week follow-up phase after treating by ICS/LABA for 3 months. Overall, the best treatment of CVA is not yet clear.

GINA 2018 emphasize that asthma need long-term management. Euro-SMART study found that budesonide/formoterol 2 inhalation twice daily plus as needed can reduce daytime asthma symptoms and night-time awakenings, as well as reduce exacerbation risk more than 1 inhalation twice daily. Based on the above reasons, We assume that increase the dosage of ICS/LABA can decrease relapse rate in CVA patients with severe cough. This multi-center, randomized, controlled clinical trial can help to clarify the best dosage of budesonide/formoterol of CVA in China.

Study Overview

• Status: Recruiting
• Conditions: Cough Variant Asthma
• Intervention / Treatment: Drug: budesonide/formoterol

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Wen Li, Prof.; Phone Number: 86-571-87783570; Email: liwenzjhz0408@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • the Second Affiliated Hospital of Zhejiang University School of Medicin
      • Contact: Wen Li, Prof.
      • Principal Investigator: Huahao Shen, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatients, with age ≥18，≤70 years old.
• Diagnose with CVA
• CSS(cough symptom score, daytime + nighttime) ≥ 3 points

Exclusion Criteria:

• Participated in any interventional clinical trial during the last 90 days.
• Pregnancy
• Associated with a clear history of other lung diseases, or combined with other systems severe illness.
• A abuse history of alcohol or narcotic drug, or have a mental history, confrontation personality, adverse motives, suspicious or other emotional or intellectual problems that may affect the informed validity of the study
• With a history of upper respiratory tract infection acute exacerbation within 4 weeks before enrolment.
• Clinical abnormalities associated with symptoms in chest radiology.
• Smokers
• On medications of ACEI or ARB
• Not suitable for study observation judged by investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Controlled group; Controlled group: budesonide/formoterol(SYM) 160/4.5ug 1 inhalation bid* 3 months (n=250).	Drug: budesonide/formoterol; apply different dosage of budesonide/formoterol in two groups and evaluate the treatment effects.
Experimental: Study group; Study group: SYM 160/4.5ug 2 inhalation bid* 3 months (n=250).	Drug: budesonide/formoterol; apply different dosage of budesonide/formoterol in two groups and evaluate the treatment effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of CVA patient with symptom relapse	Relapse rate during the 6-months' follow-up phase after treating by different doses of budesonide/formoterol for 3 months.	during 6-months' follow-up phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of CVA patient with symptom relief	symptom relief rate after treating by different doses of budesonide/formoterol for 3 months.	after treating by different doses of budesonide/formoterol for 3 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in lung function	value of pulmonary function index such as FEV1% Pred, FVC% Pred, PD20-FEV1 and PEF	during 6-months' follow-up phase
assess different phenotypes of CVA	investigate inflammation characteristics consist of differential count of inflammatory cells in induced sputum	during 6-months' follow-up phase
assess safety of different doses of budesonide/formoterol	evaluate adverse events of different doses of budesonide/formoterol	during 6-months' follow-up phase

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Tongji Hospital; Shenzhen People's Hospital; China-Japan Friendship Hospital; Central South University; Shanghai Tongji Hospital, Tongji University School of Medicine; Zunyi Medical College
• Investigators: Principal Investigator: Huahao Shen, Prof., the Second Affiliated Hospital of Zhejiang University School of Medicin

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: April 21, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2020
• Last Update Submitted That Met QC Criteria: May 9, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Respiration Disorders; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Cough; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate
• Other Study ID Numbers: ESR-17-13270

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