A Phase IIIB, 6-Month, Double-blind, Double-dummy, Randomized, Parallel-group, Multicenter Exacerbation Study of Symbicort® Pressurized Metered-Dose Inhaler (pMDI) 160/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler 4.5 μg x 2 Inhalations Twice-daily in Cronic Obstructive Pulmonary Disease (COPD) Patients.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 2,026
- 试验地点
- 1
- 主要终点
- The Rate of Moderate and Severe COPD Exacerbations Defined as: Worsening of ≥2 Major Symptoms or Worsening of 1 Major Symptom Together With ≥1 Minor Symptom for ≥2 Consecutive Days
研究概览
简要总结
Comparing the efficacy of Symbicort® pMDI and Formoterol Turbuhaler in reducing exacerbations in patients with Chronic Obstructive Pulmonary Disease (COPD).
详细描述
A Phase IIIB, 6-Month, Double-blind, Double-dummy, Randomized, Parallel-group, Multicenter Exacerbation Study of Symbicort® pMDI 160/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler 4.5 μg x 2 Inhalations Twice-daily in COPD Patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A current clinical diagnosis of COPD with COPD symptoms for more than 1 year, according to the GOLD guidelines.
- •Current or previous smoker with a smoking history equivalent to 10 or more pack years (1 pack year = 20 cigarettes smoked per day for 1 year).
- •Post-bronchodilator FEV1/forced vital capacity (FVC) <0.7 (70%) and FEV1 ≤70% of predicted normal (PN) value.
- •Documented use of a short-acting inhaled bronchodilator (β2-agonists or anticholinergics) as rescue medication within 6 months prior to study start.
- •A score of ≥2 on the modified medical research council (MMRC) dyspnea scale.
- •Documented history of ≥1 moderate or severe COPD exacerbation(s) that required treatment with systemic (oral, IM, IV) corticosteroids (a minimum 3 day course of an oral corticosteroid treatment or single depot corticosteroid injection), or hospitalization (defined as an inpatient stay or >24 hour stay in an observation area in the emergency department or other equivalent facility depending on the country and healthcare system) within 2-52 weeks before Visit 1 (i.e., not within the 14 days prior to Visit 1). A history of an exacerbation treated exclusively with antibiotics will not be considered adequate.
排除标准
- •A history of asthma at or after 18 years of age.
- •Subjects with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure (including significant cor pulmonale), uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator.
- •Known homozygous alpha-1 antitrypsin deficiency.
- •Any significant disease or disorder (e.g., gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results of the study, or the subject's ability to participate in the study.
- •A history of malignancy (except basal cell carcinoma) within the past 5 years.
- •Active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, or other active pulmonary diseases.
- •Subjects who have needed additions or alterations to their usual maintenance or change in formulation of rescue therapy for COPD due to worsening symptoms within the 14 days prior to Visit 1 and up to Visit
- •CXR (frontal and lateral) with suspicion of pneumonia or other condition/abnormality that will require additional investigation/treatment, or put the subject at risk because of participation in the study.
- •Risk factors for pneumonia: immune suppression (HIV, lupus) or other risk for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson's disease, myasthenia gravis, etc.).
- •Pneumonia not resolved within 14 days of Visit
- •Moderate or severe COPD exacerbation that has not resolved within 14 days prior to Visit 1 or a moderate or severe COPD exacerbation that occurs between Visit 1 and Visit
- •Long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day.
- •Subjects who are currently in the intensive rehabilitation phase or scheduled to begin new participation (intensive rehabilitation phase) in a pulmonary rehabilitation program during the study or have started a new pulmonary rehabilitation program within 60 days of Visit
- •Subjects in the maintenance phase of pulmonary rehabilitation program are not excluded.
- •Treatment with oral, parenteral, or intra-articular corticosteroids within 4 weeks prior to Visit
- •Omalizumab or any other monoclonal or polyclonal antibody therapy taken for any reason within 6 months prior to Visit 1.
研究组 & 干预措施
Symbicort pMDI
Symbicort pMDI, budesonide/formoterol, 160/4.5 μg x 2 actuations BID, for oral inhalation
干预措施: Symbicort (Drug)
Symbicort pMDI
Symbicort pMDI, budesonide/formoterol, 160/4.5 μg x 2 actuations BID, for oral inhalation
干预措施: Placebo for Symbicort pMDI (Other)
Formoterol Turbuhaler
Formoterol Turbuhaler, 4.5 μg x 2 actuations BID, for oral inhalation
干预措施: Formoterol turbohaler (Drug)
Formoterol Turbuhaler
Formoterol Turbuhaler, 4.5 μg x 2 actuations BID, for oral inhalation
干预措施: Placebo for Formoterol Turbohaler (Other)
结局指标
主要结局
The Rate of Moderate and Severe COPD Exacerbations Defined as: Worsening of ≥2 Major Symptoms or Worsening of 1 Major Symptom Together With ≥1 Minor Symptom for ≥2 Consecutive Days
时间窗: Randomization at Week 0 to End of Treatment (EoT) W 26
The annual COPD exacerbation rate was analyzed and compared between two arms. Annual exacerbation rate for each subject is defined as number of exacerbations divided by duration of randomized treatment period in years. The annual COPD exacerbation rate of Symbicort group was compared with annual rate of Formoterol group. The rate ratio of Symbicort vs. Formoteroal was assessed by a negative binomial model. Exacerbations, that met the modified Anthonisen criteria and duration ≥2 days were classified as moderate and severe exacerbations. Moderate exacerbation: treatment of symptoms with systemic corticosteroids (≥3 days) and/or antibiotics. Severe exacerbation: symptoms that require hospitalization (including \>24 hours in ED/urgent care setting).
次要结局
- Pre-dose/Pre-bronchodilator FEV1 at the Study Site(From Run-in W -4 to EoT W 26)
- St. George's Respiratory Questionnaire (SGRQ)(From Run-in W -4 to EoT W 26)
- Number of Patients With Moderate or Severe COPD Exacerbation.(From randomzation to EoT W 26)
- Total Rescue Medication Use (Average Puffs/Day)(From Run-in W -4 to EoT W 26)
- Nights With Awakening Due to COPD(From Run-in W -4 to EoT W 26)