The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis

Condition(s) targeted: Bronchiectasis

Intervention: Formoterol-budesonide (Drug); Theophylline (Drug); Placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: The First Affiliated Hospital of Guangzhou Medical University

Official(s) and/or principal investigator(s):
Chen Rongchang, Professor, Study Director, Affiliation: institute vice director
Zhong Nanshan, Professor, Study Director, Affiliation: institute director

The purpose of this study is to examine the efficacy and safety of 24 weeks treatment with theophylline plus low-dose formoterol-budesonide in subjects with bronchiectasis.

Official title: The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Quality of Life Assessment with St George's Respiratory Questionnaire(SGRQ) and Leicester Cough Questionnaire(LCQ)

Secondary outcome:

Mean number of exacerbations per patient per 24 weeks

Changes of sputum characteristics from baseline to 24 weeks

Changes of 24 hour sputum volume from baseline to 24 weeks

Changes of forced expiratory volume in 1 second(FEV1) from baseline to 24 weeks

Changes of mean forced expiratory flow between 25% and 75% of the FVC(FEF25-75)from baseline to 24 weeks

Changes of forced vital capacity(FVC) from baseline to 24 weeks

Changes of peak expiratory flow(PEF) from baseline to 24 weeks

Induced sputum cytology count

Changes of sputum culture from baseline to 24 weeks

IL-6

IL-8

IL-10

Tumor necrosis factor(TNF)α

Activity of histone deacetylase(HDAC)

Activity of histone acetyltransferase(HAT)

8-Isoprostane

Neutrophilic granulocytes in blood routine examination

White blood cells in blood routine examination

Monocytes in blood routine examination

Eosinophilic granulocytes in blood routine examination

Number of participants with Adverse events as a measure of safety and tolerability

Plasma Concentration of Theophylline

Detailed description: Non-cystic fibrosis bronchiectasis is an orphan disease caused by the pathogenic vicious circle including infection, inflammation and airway repair. Today's principle of treatment is to break the cycle of inflammation and infection. Nowadays, most clinical trials are anti-infective treatment by antibiotics trying to break this cycle by reducing the bacterial load, which may cause bacterial resistance. There were still some anti-inflammation trials by using inhaled corticosteroids(ICS). Tsang and Martínez-García showed that inhaled corticosteroids reduced IL-1,IL-8 levels and sputum inflammation cells, and improved sputum volume as well as quality of life, though the corticosteroid must be high dose or medium dose combined with long-acting ß2 adrenergic agonists. As described in asthma and chronic obstructive pulmonary disease(COPD), theophylline can improve the activity of histone deacetylase (HDAC) and then enhanced the anti-inflammatory effect of steroids. We hypothesis that theophylline may have the same effect in subjects with bronchiectasis. Theophylline plus inhaled low-dose formoterol-budesonide may improve quality of life and reduce airway inflammation.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients between 18-70 years old with non-cystic fibrosis(CF) bronchiectasis, free

from acute exacerbations for at least 3 months. Stable phase of the disease. Exclusion Criteria:

- Patients with a cigarette smoking history of more than 10 packs-year. Patients with

COPD. Patients with traction bronchiectasis due to advanced fibrosis. Patients with known intolerance for theophylline. Patients with asthma. Patients with other disease disturbing outcomes of the trials. Patients without consent.

State Key Laboratory of Respiratory Research Institute., Guangzhou City, Guangdong 510000, China

The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, China

Starting date: July 2013
Last updated: March 10, 2015