Evaluate the Effect of Aclidinium Bromide on Long-term Cardiovascular Safety and Exacerbations in Moderate to Very Severe COPD Patients.
Condition: COPD; Chronic Obstructive Pulmonary Disease; Moderate to Very Severe COPD
MeSH terms: Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive
Intervention: Aclidinium Bromide; Placebo
Intervention description: 400 μg, twice per day, oral administration via a multi-dose dry-powder inhaler (DPI); Dose matched placebo, twice per day, oral administration via a multi-dose dry-powder inhaler (DPI)
Intervention MeSH terms: Bromides
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3635.0
Sex: All
Minimum age: 40 Years
Maximum age: 130 Years
Healthy volunteers: No

Summary:

      The Objectives of this study are to assess the safety of Aclidinium bromide on major adverse
      cardiovascular events (MACE), to assess the overall safety of Aclidinium bromide and to
      assess whether Aclidinium bromide reduces moderate or severe COPD exacerbations. This study
      is a double-blind, randomized, placebo controlled, parallel-group study to evaluate the
      effect of Aclidinium bromide on the cardiovascular safety and COPD exacerbations in patients
      with moderate to very severe COPD, as defined by the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) criteria.
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. Male or female outpatients ≥ 40 years of age

          -  2. Current or former cigarette smokers with a smoking history of at least 10
             pack-years

          -  3. A diagnosis of stable, moderate to very severe COPD (GOLD, 2015) with a
             post-bronchodilator FEV < 80% FEV1/forced vital capacity (FVC) ratio < 70%

          -  4. Must have at least one of the following 4 criteria:

               1. Documented cerebrovascular disease (stroke or transient ischemic attack, carotid
                  stenosis)

               2. Documented coronary artery disease (angina, MI, angioplasty/stent/bypass)

               3. Documented peripheral vascular disease or history of claudication

               4. At least 2 of the following atherothrombotic risk factors as determined by the
                  PI:

                    1. Male ≥ 65 years or female ≥ 70 years

                    2. Diabetes

                    3. Dyslipidemia

                    4. Hypertension

                    5. Waist circumference inches males ≥ 40 in or in females ≥ 38 inches

                    6. Evidence of renal dysfunction (eGFR < 60) and microalbuminuria (eGFR is
                       based on modification of diet in renal disease [MDRD] equation,
                       microalbuminuria is defined as ≥ 30-300 mcg/mg creatinine on a spot urine or
                       ≥30 mg creatinine on a 24hr urine test)

          -  5. Maintained stable respiratory medications for 2 weeks prior to randomization
             (Appendix II)

          -  6. Able to perform pulmonary function test (PFT) maneuvers and follow study procedures

          -  7. Women of childbearing potential must have a negative serum β-human chorionic
             gonadotropin (HCG) pregnancy test at Visit 1A and be practicing medically acceptable
             method of contraception. Otherwise, female patients should be at least 1 year
             postmenopausal, surgically sterile (defined as having a hysterectomy or tubal
             ligation).

          -  8. Should understand study procedures and be willing to participate in the study as
             indicated by signing the ICF

        Exclusion Criteria:

          -  1. Significant diseases other than COPD or cardiovascular disease (e.g., metastatic
             cancer) which, in the opinion of the PI, may either put the patient at risk because of
             participation in the study or a disease which may influence the results of the study
             or the patient's ability to participate in the study

          -  2. Unstable or life threatening cardiovascular disease or COPD as determined by the PI

          -  3. Patients with comorbid lung disease such as asthma, cystic fibrosis,
             bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease

          -  4. Planned lung transplant or lung volume reduction surgery

          -  5. Currently treated with a combination of LAMA and LABA/ICS therapy.

          -  6. Malignancy for which patient has undergone resection, radiation therapy or
             chemotherapy within 5 years prior to screening. Patients with treated basal cell and
             squamous cell (skin) carcinoma are allowed

          -  7. Respiratory infection or COPD exacerbation at Screening and/or within 4 weeks prior
             to screening

          -  8. Uncontrolled infection resulting from human immunodeficiency virus (HIV) and/or
             active hepatitis

          -  9. Reported history of drug or alcohol abuse within the past 12 months

          -  10. History of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic
             amines, or inhaled medication or any component thereof (including report of
             paradoxical bronchospasm)

          -  11. History of acute urinary retention, treatment refractory benign prostatic
             hyperplasia (BPH), bladder neck obstruction, or narrow-angle glaucoma (Note: Patients
             with controlled, stable BPH are not excluded)

          -  12. Patients unable to use a multidose DPI or a pressurized metered-dose inhaler

          -  13. Treatment with any other investigational drug within 30 days (or 6 half-lives,
             whichever is longer) before Visit 1A

          -  14. Women who are pregnant or breastfeeding

          -  15. Use of any prohibited medication listed in Appendix II

          -  16. Employee or immediate relative of an employee of AstraZeneca, any of its
             affiliates or partners, or the study center