慢性阻塞性肺部疾病

主要 本試驗的主要目的在於前瞻性地評估1天1次Fluticasone Furoate (FF)/Vilanterol (VI)吸入型粉劑100/25mcg，相較於安慰劑，對於患有中度COPD (預測的FEV1≥50、≤70%)且有心血管疾病病史或心血管疾病風險增加的受試者存活率的影響。 次要 次要目標包括： • 評估FF/VI對於FEV1降低速度的影響，與安慰劑進行比較。 1. • 評估FF/VI對於包含治療期間心血管疾病(CV)造成的死亡、心肌梗塞、中風、不穩定心絞痛及短暫性腦缺血(TIA)等心血管複合試驗指標的影響，與安慰劑進行比較。 其他目標包括： • 針對所有主要、次要、其他與探索性指標進行下列治療比較： 比較FF/VI與FF 比較FF/VI與VI 比較FF與安慰劑 比較VI與安慰劑 • 與安慰劑進行比較評估FF/VI對於中度/重度COPD惡化速度的影響。 • 與安慰劑進行比較評估FF/VI對於COPD相關死亡率的影響。 • 與安慰劑進行比較評估FF/VI對於在某特定族群的受試者動脈硬化的影響。 • 與安慰劑進行比較評估FF/VI對於在某特定族群的受試者健康相關生活品質的影響(使用SGRQ-C進行評估)。 • 按治療組別針對在某特定族群的受試者使用歐洲生活品質問卷(EQ-5D)蒐集到的健康狀況數據評估調整品質後的存活年份(QALY)。 • 與安慰劑進行比較評估FF/VI對於醫療資源利用率的影響(根據因COPD住院 的天數進行衡量)。 探索性目的包括： • 與安慰劑進行比較評估FF/VI對於在某特定族群的受試者COPD健康狀況的影響(使用COPD評估工具，CAT)。 • 與安慰劑進行比較檢視血液檢體的分子組成，找出可能影響對於FF/VI的生物與臨床反應及/或與罹患COPD或COPD惡化相關或醫療相關情況的因子。 • 檢視比較性指標預測死亡率的能力

Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg

Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg

Inhalation Powder

100/25

主要療效指標

• 從治療開始到任何原因死亡所需的時間
次要療效指標

• FEV1降低速度
• 自治療開始至出現心血管疾病(CV)事件所需的時間
其他療效指標
• 中度/重度COPD年惡化速度
• 自治療開始至出現COPD相關死亡所需的時間(根據CEC的裁定)
• 生活品質問卷(使用聖喬治呼吸問卷-COPD)
• 健康狀況問卷(使用歐洲生活品質問卷，EQ-5D)
• 醫療資源利用率
• 脈搏波速測量(PWV)
探索性指標

• 健康狀況(使用CAT評估)
• 生物標記
• 臨床實驗室檢驗

Inclusion Criteria:
1. Type of subject: outpatient.
2. Informed consent: Subjects must give their signed and dated written informed
consent to participate.
3. Gender: Male or female. Female subjects must be post-menopausal or using a highly
effective method for avoidance of pregnancy. The decision to include or exclude
women of childbearing potential may be made at the discretion of the investigator in
accordance with local practice in relation to adequate contraception.
4. Age: ≥40 and ≤ 80 years of age at Screening (Visit 1).
5. Tobacco use: Subjects with a current or prior history of ≥10 pack-years of cigarette
smoking at screening (Visit 1). Previous smokers are defined as those who have
stopped smoking for at least 6 months prior to Visit 1.
6. Airflow Obstruction:
• Subjects with a measured post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 at
Screening (Visit 1).
• Subjects with a measured post-albuterol/salbutamol FEV1 ≥50 and ≤70% of
predicted normal values calculated using NHANES III reference equations
[Hankinson, 1999; Hankinson, 2010] at Screening (Visit 1).
Post-bronchodilator spirometry will be performed approximately 15 minutes
after the subject has self-administered 4 inhalations (i.e., total 400mcg) of
albuterol/salbutamol via an MDI with a valved-holding chamber. The
FEV1/FVC ratio and FEV1 percent predicted values will be calculated.
7. Dyspnea:
Subjects must score 2 or higher on the modified Medical Research Council Dyspnea
scale (Visit 1)

8. Cardiovascular disease:
For patients >= 40 years of age: any one of the following:
Established (i.e. by clinical signs or imaging studies) coronary artery
disease (CAD)
Established (i.e. by clinical signs or imaging studies) peripheral vascular
disease (PVD)
Previous stroke
Previous MI
Diabetes mellitus with target organ disease
OR
For patients >=60 years of age: any 2 of the following:
Being treated for hypercholesterolemia
Being treated for hypertension
Being treated for diabetes mellitus
Being treated for peripheral vascular disease

Exclusion Criteria:
1. Pregnancy: Women who are pregnant or lactating.
2. Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of
asthma are eligible if they also have a current diagnosis of COPD).
3. α
-antitrypsin deficiency: Subjects with known α-1 antitrypsin deficiency as the
underlying cause of COPD.
4. Other respiratory disorders: Subjects with active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial
lung diseases or other active pulmonary diseases.
5. Lung resection or transplantation: Subjects with lung volume reduction surgery
within the 12 months prior to Screening or having had a lung transplant.
6. A moderate/severe COPD exacerbation that has not resolved at least 14 days prior
to Visit 1 and at least 30 days following the last dose of oral corticosteroids (if
applicable).
7. Current severe heart failure (New York Heart Association class IV). Subjects will
also be excluded if they have a known ejection fraction of <30% or if they have an
implantable cardioverter defibrillator (ICD).
8. Other diseases/abnormalities: Any life-threatening condition with life expectancy
<3 years, other than vascular disease or COPD, that might prevent the subject from
completing the study.
9. End stage chronic renal disease: Subjects will be excluded if on renal replacement
therapy (hemodialysis or peritoneal).
10. Drug/food allergy: Subjects with a history of hypersensitivity to any of the study
medications (e.g. beta-agonists, corticosteroid) or components of the inhalation
powder (e.g. lactose, magnesium stearate). In addition, patients with a history of
severe milk protein allergy that, in the opinion of the study physician, contraindicates
the subject’s participation will also be excluded.
11. Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
abuse within the last 2 years.
12. Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy
(LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day.
Oxygen prn use (i.e. ≤12 hours per day) is not exclusionary.
13. Questionable validity of consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation or other conditions that will limit the validity
of informed consent to participate in the study or the potential compliance to study
procedures.
14. Affiliation with investigator site: Study investigators, sub-investigators, study
coordinators, employees of a participating investigator or immediate family members
of the aforementioned are excluded from participating in this study.
15. Additional medication: