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Evaluate the Effect of Aclidinium Bromide on Long-term Cardiovascular Safety and Exacerbations in Moderate to Very Severe COPD Patients. (ASCENT COPD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01966107
First received: October 16, 2013
Last updated: September 14, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
COPD
Chronic Obstructive Pulmonary Disease
Moderate to Very Severe COPD
Drug: Aclidinium Bromide
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-blind, Randomized, Placebo-controlled, Parallel-group, Phase IV Study to Evaluate the Effect of Aclidinium Bromide on Long-term Cardiovascular Safety and COPD Exacerbations in Patients With Moderate to Very Severe COPD (ASCENT COPD)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Time to first Major Adverse Cardiovascular Event (MACE) [ Time Frame: up to 36 months ] [ Designated as safety issue: Yes ]
  • Rate of moderate or severe COPD exacerbations per patient per year during the first year of treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of hospitalizations due to COPD exacerbation per patient per year during the first year of treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Time to first Major Adverse Cardiovascular Event (MACE) or other serious cardiovascular events of interest [ Time Frame: up to 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 4000
Study Start Date: October 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aclidinium Bromide
Two-week washout/run-in period [for patients on a long-acting muscarinic antagonist (LAMA)] followed by a maximum of 36-month double-blind treatment period.
Drug: Aclidinium Bromide
400 μg, twice per day, oral administration via a multi-dose dry-powder inhaler (DPI)
Placebo Comparator: Placebo
Two-week washout/run-in period [for patients on a long-acting muscarinic antagonist (LAMA)] followed by a maximum of 36-month double-blind treatment period.
Drug: Placebo
Dose matched placebo, twice per day, oral administration via a multi-dose dry-powder inhaler (DPI)

  Eligibility

Ages Eligible for Study:   40 Years to 130 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01966107

  Show 384 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Kenneth R. Chapman, MD MSc FRCPC FACP FCCP GSK-CIHR Research Chair in Respiratory Health Care Delivery,
Principal Investigator: Robert Wise, MD Johns Hopkins Bayview Medical Center, Asthma and Allergy Center
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01966107     History of Changes
Other Study ID Numbers: D6560C00002  LAS-MD-45 
Study First Received: October 16, 2013
Last Updated: September 14, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Bromides
Muscarinic Antagonists
Anticonvulsants
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 28, 2016