The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo+formoterol-budesonide Placebo(for Theophylline sustained-release tablet) tablet by mouth 100mg every 12hours for 24weeks. Inhaled Formoterol-budesonide combined treatment 4.5µg/160µg every 12hours for 24weeks. |
Drug: Formoterol-budesonide
Formoterol-budesonide combined treatment (4.5µg/160µg Q12H)
Other Names:
Drug: Placebo
Placebo for theophylline 0.1 Q12H
|
| Experimental: Theophylline+formoterol-budesonide Theophylline sustained-release tablet by mouth 100mg every 12hours for 24weeks. Inhaled formoterol-budesonide combined treatment 4.5µg/160µg every 12hours for 24weeks. |
Drug: Formoterol-budesonide
Formoterol-budesonide combined treatment (4.5µg/160µg Q12H)
Other Names:
Drug: Theophylline
Theophylline 0.1 Q12H
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Quality of Life Assessment with St George's Respiratory Questionnaire(SGRQ) and Leicester Cough Questionnaire(LCQ) [Baseline and 24 weeks]
Secondary Outcome Measures
- Mean number of exacerbations per patient per 24 weeks [Baseline and 24 weeks]
Exacerbations defined by persistent (≥ 24 h) deterioration in at least three respiratory symptoms, including cough, dyspnea, hemoptysis, increased sputum purulence or volume, chest pain (with or without fever).
- Changes of sputum characteristics from baseline to 24 weeks [Baseline and 24 weeks]
- Changes of 24 hour sputum volume from baseline to 24 weeks [Baseline and 24 weeks]
- Changes of forced expiratory volume in 1 second(FEV1) from baseline to 24 weeks [Baseline and 24 weeks]
- Changes of mean forced expiratory flow between 25% and 75% of the FVC(FEF25-75)from baseline to 24 weeks [Baseline and 24 weeks]
- Changes of forced vital capacity(FVC) from baseline to 24 weeks [Baseline and 24 weeks]
- Changes of peak expiratory flow(PEF) from baseline to 24 weeks [Baseline and 24 weeks]
- Induced sputum cytology count [Baseline and 24 weeks]
- Changes of sputum culture from baseline to 24 weeks [Baseline and 24 weeks]
- IL-6 [Baseline and 24 weeks]
Test IL-6 both in blood and sputum.
- IL-8 [Baseline and 24 weeks]
Test IL-8 both in blood and sputum.
- IL-10 [At 24 weeks]
Test IL-10 both in blood and sputum.
- Tumor necrosis factor(TNF)α [Baseline and 24 weeks]
Test TNF-α both in blood and sputum.
- Activity of histone deacetylase(HDAC) [Baseline and 24 weeks]
HDACs are extracted from cells in blood.
- Activity of histone acetyltransferase(HAT) [Baseline and 24 weeks]
HATs are extracted from cells in blood.
- 8-Isoprostane [Baseline and 24 weeks]
- Neutrophilic granulocytes in blood routine examination [Baseline and 24 weeks]
- White blood cells in blood routine examination [Baseline and 24 weeks]
- Monocytes in blood routine examination [Baseline and 24 weeks]
- Eosinophilic granulocytes in blood routine examination [Baseline and 24 weeks]
- Number of participants with Adverse events as a measure of safety and tolerability [24 weeks]
Adverse events may contain symptoms such as nausea, sickness, headache, insomnia, palpitation, arrhythmia and so on. Record the symptoms and times of the patients.
- Plasma Concentration of Theophylline [24 weeks]
Venous blood was taken for plasma theophylline at the end of the treatment period. (At the very time of 2 hours after patients taken the pills)
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | State Key Laboratory of Respiratory Research Institute. | Guangzhou City | Guangdong | China | 510000 |
| 2 | The First Affiliated Hospital of Guangzhou Medical University | Guangzhou | Guangdong | China | 510000 |
Sponsors and Collaborators
- The First Affiliated Hospital of Guangzhou Medical University
Investigators
- Study Director: Chen Rongchang, Professor, institute vice director
- Study Director: Zhong Nanshan, Professor, institute director
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- theophylline in bronchiectasis