HZCL13782: a CLÍNICAL OUTCOMES STUDY TO COMPARE THE EFFECT OF FLUTICASONE FUROATE/VILANTEROL INHALATION POWDER 100/25 MCG WITH PLACEBO ON SURVIVAL IN SUBJECTS WITH MODERATE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND A HISTORY OF OR AT INCREASED RISK FOR CARDIOVASCULAR DISEASE

INTERVENTION: SUBJECTS WILL BE RANDOMIZED TO TREATMENT AFTER A 4‐10 DAY RUN‐IN PERIOD. PRIOR TO RUN‐IN, SUBJECTS WILL DISCONTINUE USE OF PREVIOUS COPD MEDICATIONS EXCEPT FOR SHORT‐ACTING BRONCHODILATORS AND THEOPHYLLINES. CLINIC VISITS WILL OCCUR AT SCREENING, RANDOMIZATION, 4 WEEKS AND THEN EVERY 12 WEEKS UNTIL THE STUDY HAS REACHED THE REQUIRED NUMBER OF EVENTS. A SAFETY FOLLOW‐UP PHONE CONTACT WILL OCCUR 1 WEEK AFTER COMPLETING EITHER RANDOMIZED TREATMENT OR AN EARLY WITHDRAWAL OF INVESTIGATIONAL PRODUCT. FOLLOWING THE RUN‐IN PERIOD, ELIGIBLE SUBJECTS WILL BE RANDOMIZED (1:1:1:1) TO ONE OF THE FOLLOWING DOUBLE‐BLIND TREATMENT GROUPS. ALL TREATMENTS WILL BE DELIVERED VIA THE NOVEL ORY POWDER INHALER (NDPI) ONCE DAILY IN THE AM DURING THE TREATMENT PERIOD (WITH THE POSSIBLE EXCEPTION OF THE RANDOMIZATION VISIT): • FF/VI 100 MCG/25 MCG QD • FF 100 MCG QD • VI 25 MCG QD • PLACEBO QD CONDITION: PRIMARY OUTCOME: Primary efficacy end‐point of time to all‐cause mortality; NAME OF THE RESULT: Primary efficacy end‐point of time to all‐cause mortality; USED MEASURING METHOD :Cox proportional hazards regression model.; PERIOD OF TIME WHERE THE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Approximately 15 to 44 months SECONDARY OUTCOME: Rate of decline of absolute trough FEV1 recorded during the treatment period ; NAME OF THE RESULT: Rate of decline of absolute trough FEV1 recorded during the treatment period ; USED MEASURING METHOD :Random coefficients model ; PERIOD OF TIME WHERE THE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE SECONDARY RESULT: Approximately 15 to 44 months 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 Ͱ