Chronic Obstructive Pulmonary Disease (COPD) Post-hospitalization Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01110200
First received: April 22, 2010
Last updated: July 10, 2014
Last verified: June 2013
  Purpose

This trial is a randomized, double-blind, parallel-group, multicenter study to be conducted in the United States. The purpose of the study is to evaluate the rate of exacerbations of chronic obstructive pulmonary disease (COPD) following hospital discharge for an acute exacerbation of COPD, in patients receiving either fluticasone propionate/salmeterol combination product 250/50mcg BID or salmeterol 50mcg BID via DISKUS™ over 29 weeks. The study population will include patients hospitalized for an acute exacerbation of COPD. The target enrolment is 720 subjects at 80 study centers. The primary endpoint is the rate of exacerbation requiring hospitalization that occur more than 21 days post-discharge, emergency room visit or physician's office visit for an exacerbation of COPD requiring treatment with oral corticosteroids or oral corticosteroids and antibiotics. The secondary endpoint is the rate of COPD exacerbation requiring treatment with oral corticosteroids, antibiotics, and/or hospitalization (alone and in combination). Related efficacy endpoints include, time to first exacerbation of COPD requiring treatment with oral corticosteroids, antibiotics, and/or hospitalization (alone and in combination), pre-dose AM FEV1, the probability of premature withdrawal of subject from the study, and supplemental albuterol use, change in biomarkers of inflammation, including, surfactant protein D (SP-D), clara cell secretory protein 16 (CC-16) and high sensitivity C-reactive protein (hs-CRP). Health outcome assessments include domain scores evaluation for fatigue, dyspnea, emotional function and mastery, measured with the Chronic Respiratory Disease Questionnaire self-administered standardized format (CRQ-SAS); and symptoms (congestion, cough, phlegm, mucus, chest discomfort, shortness of breath and sleep disturbance), assessed by the EXAcerbations of Chronic pulmonary disease Tool (EXACT). Albuterol will be supplied to study subjects for use as-needed throughout the study. Safety will be assessed by monitoring of adverse events.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: ADVAIR DISKUS 250/50 mg BID
Drug: SEREVENT 50 mcg BID
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: A Randomized, Double-Blind, Parallel Group, Multicenter Study of the Effects of Fluticasone Propionate/Salmeterol Combination Product 250/50mcg BID (ADVAIR DISKUS™) in Comparison to Salmeterol 50mcg BID (SEREVENT DISKUS™) on the Rate of Exacerbations of COPD Following Hospitalization

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Par. With Chronic Obstructive Pulmonary Disease (COPD) EXs Requiring Hospitalization That Occurred >21 Days Post-discharge/Physician's Office Visit for a COPD EX Requiring Treatment With Oral Corticosteroids (OCSs) or OCSs and Antibiotics (ABs) [ Time Frame: From 21 days post-discharge (hospital or emergency room) or physician's office visit, up to 29 weeks ] [ Designated as safety issue: No ]
    A COPD exacerbation (EX) was defined as the worsening of >=2 major symptoms (dyspnoea, sputum volume, sputum purulence [containing/discharging pus]) or the worsening of any 1 major symptom together with any 1 minor symptom (sore throat, cold [nasal discharge and/or nasal conjestion], fever without other cause, increased cough or wheeze) for at least 2 consecutive days. COPD EXs were identified by symptom review, and/or were based on investigator judgment (via phone contact or at a clinic visit). Hospitalization had to occur >21 days post-discharge/physician's office visit for a prior COPD EX.

  • Number of Participants With the Indicated Number of EXs of COPD Requiring Hospitalization That Occurred More Than 21 Days Post-discharge or Physician's Office Visit for an EX of COPD Requiring Treatment With OCSs or OCSs and ABs [ Time Frame: From 21 days post-discharge (hospital or emergency room) or physician's office visit, up to 29 weeks ] [ Designated as safety issue: No ]
    A COPD EX was defined as the worsening of >=2 major symptoms (dyspnoea, sputum volume, sputum purulence [containing/discharging pus]) or the worsening of any 1 major symptom together with any 1 minor symptom (sore throat, cold [nasal discharge and/or nasal conjestion], fever without other cause, increased cough or wheeze) for at least 2 consecutive days. COPD EXs were identified by symptom review, and/or were based on investigator judgment (via phone contact or at a clinic visit). Hospitalization had to occur more than 21 days post-discharge or physician's office visit for a prior COPD EX.

  • Number of EXs of COPD Requiring Hospitalization That Occurred More Than 21 Days Post-discharge or Physician's Office Visit for an EX of COPD Requiring Treatment With OCSs or OCSs and ABs [ Time Frame: From 21 days post-discharge (hospital or emergency room) or physician's office visit, up to 29 weeks ] [ Designated as safety issue: No ]
    A COPD EX was defined as the worsening of >=2 major symptoms (dyspnoea, sputum volume, sputum purulence [containing/discharging pus]) or the worsening of any 1 major symptom together with any 1 minor symptom (sore throat, cold [nasal discharge and/or nasal conjestion], fever without other cause, increased cough or wheeze) for at least 2 consecutive days. COPD EXs were identified by symptom review, and/or were based on investigator judgment (via phone contact or at a clinic visit). Hospitalization had to occur more than 21 days post-discharge or physician's office visit for a prior COPD EX.


Secondary Outcome Measures:
  • Number of Participants With an EX of COPD Requiring Treatment With OCSs, Treatment With ABs, and/or Hospitalization [ Time Frame: From Baseline up to Week 29, approximately ] [ Designated as safety issue: No ]
    A COPD EX was defined as the worsening of >=2 major symptoms (dyspnoea, sputum volume, sputum purulence [containing/discharging pus]) or the worsening of any 1 major symptom together with any 1 minor symptom (sore throat, cold [nasal discharge and/or nasal conjestion], fever without other cause, increased cough or wheeze) for at least 2 consecutive days. COPD EXs were identified by symptom review, and/or were based on investigator judgment (via phone contact or at a clinic visit).

  • Number of EXs of COPD Requiring Treatment With OCSs, Treatment With ABs, and/or Hospitalization (Alone and in Combination) [ Time Frame: From Baseline up to Week 29, approximately ] [ Designated as safety issue: No ]
    A COPD EX was defined as the worsening of >=2 major symptoms (dyspnoea, sputum volume, sputum purulence [containing/discharging pus]) or the worsening of any 1 major symptom together with any 1 minor symptom (sore throat, cold [nasal discharge and/or nasal conjestion], fever without other cause, increased cough or wheeze) for at least 2 consecutive days. COPD EXs were identified by symptom review, and/or were based on investigator judgment (via phone contact or at a clinic visit).


Enrollment: 639
Study Start Date: April 2010
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ADVAIR DISKUS 250/50 mcg BID
Fluticasone propionate/salmeterol 250/50 mcg BID in the DISKUS formulation (ADVAIR DISKUS) is a combination product containing a corticosteroid and a long-acting beta2-adrenergic agonist, indicated in the US for the maintenance treatment of airflow obstruction and reducing exacerbations in patients with COPD.
Drug: ADVAIR DISKUS 250/50 mg BID
Fluticasone propionate/salmeterol 250/50 mcg BID in the DISKUS formulation (ADVAIR DISKUS) is a combination product containing a corticosteroid and a long-acting beta2-adrenergic agonist, indicated in the US for the maintenance treatment of airflow obstruction and reducing exacerbations in patients with COPD.
Other Name: FSC 250/50 mcg
Active Comparator: Serevent 50 mcg BID
Salmeterol xinafoate Inhalation Powder (SEREVENT DISKUS) is indicated for the long-term, twice-daily (morning and evening), administration in the maintenance treatment of bronchospasm associated with COPD (including emphysema and chronic bronchitis).
Drug: SEREVENT 50 mcg BID
Salmeterol xinafoate Inhalation Powder (SEREVENT DISKUS) is indicated for the long-term, twice-daily (morning and evening), administration in the maintenance treatment of bronchospasm associated with COPD (including emphysema and chronic bronchitis).
Other Name: Salmeterol xinafoate 50 mcg

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects eligible for enrolment in this study must meet all of the following criteria:

  • Male or female of at least 40 years of age at screening.

To be eligible for entry into the study, females of childbearing potential must commit to the consistent and correct use of an acceptable method of birth control starting on the day of visit 1, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days), as defined by any one of the following:

  • Abstinence Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse
  • Oral contraceptive (either combined estrogen/progestin or progestin only)
  • Injectable progestogen
  • Implants of levonorgestrel or etonogestrel
  • Percutaneous contraceptive patches
  • Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year,
  • Male partner who is sterile (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or
  • Double-barrier method; condom or occlusive cap (diaphragm or cervical /vault caps) plus spermicide.
  • Current or former smokers with a >10 pack-year cigarette smoking history [number of pack years = (number of cigarettes per day / 20) X number of years smoked (e.g., 10 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years]. Former smokers are defined as those who have quit smoking for at least 3 months prior to the screening visit.
  • Any of the following populations:
  • Patients hospitalized for a duration not exceeding 10 days due to an acute exacerbation of COPD, and who must be randomized within 10 days post-discharge.
  • Patients with COPD who were treated and held for observation in the emergency department (i.e. emergency room, ER) for at least 24 hours due to an acute exacerbation of COPD, and who must be randomized within 10 days post-discharge.
  • Patients who received oral corticosteroids or oral corticosteroids and antibiotics for treatment of an exacerbation of COPD during a physician's office visit and who must be randomized within 10 days of the visit, and who have been hospitalized within the previous six months due to an acute exacerbation of COPD.
  • Clinical diagnosis of COPD (for at least 6 months). The following definition of COPD from the American Thoracic Society (ATS) will be used: COPD is a disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyper-reactivity, and may be partially reversible [American Thoracic Society, 1995].
  • Documented evidence (within a year prior to Visit 1) in the medical chart of spirometry confirming the diagnosis of COPD and/or spirometry performed prior to randomization (Visit 2) that confirms pre-bronchodilator FEV1/FVC ratio less than or equal to 0.70 and pre-bronchodilator FEV1 <70% of predicted.
  • Review and subject's completion of written informed consent: a subject-signed and dated written informed consent (form) must be obtained prior to any study procedure, and the subject must be willing to comply with all the requirements of the study protocol.
  • Subject must be able to read, comprehend, and record information in English or Spanish.

Exclusion Criteria:

  • Subjects meeting any of the following criteria must not be enrolled in the study:
  • Diagnosis of pneumonia, congestive heart failure (CHF), or other complicating co-morbid condition while hospitalized within the last 6 months for an exacerbation of COPD.
  • Historical or current evidence of clinically significant uncontrolled disease including, but not limited to, those listed below. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subjects at risk through study participation, or which would affect the safety analysis or other analyses if the disease/condition exacerbated during the study.
  • A previous lung resection surgery (e.g. lobectomy, pneumonectomy, etc) within the year preceding Visit 1 (Screening)
  • Asthma as primary diagnosis
  • Lung cancer
  • Cystic fibrosis, pulmonary fibrosis, active tuberculosis, or sarcoidosis
  • Clinically significant cardiac arrhythmias
  • Uncontrolled hypertension
  • Unstable angina
  • Current malignancy or a previous history of cancer in remission for < 5yrs (localized basal cell or squamous cell carcinoma of the skin that has been resected is not excluded)
  • Uncontrolled diabetes mellitus
  • Uncontrolled hyperthyroidism or hypothyroidism
  • Immunologic compromise
  • Cushing's or Addison's disease
  • An abnormal 12-lead electrocardiogram (ECG) at Visit 1 (Screening) deemed to be clinically significant by the investigator.
  • A chest X-ray or computed tomography (CT) scan performed in the 6 months preceding Visit 1 that revealed evidence of clinically significant abnormalities not believed to be due to the presence of COPD. If the subject does not have a record of a chest X-ray, one must be obtained and reviewed prior to randomization.
  • Female patients with a positive urine pregnancy test at Visit 1.
  • Any infirmity, physical disability, or geographic location that would limit compliance for scheduled visits.
  • Any adverse reaction, immediate or delayed, hypersensitivity to any Beta-agonist, sympathomimetic drug, or corticosteroid including any components of the study drug formulations.
  • Limited ability to provide a valid informed consent due to psychiatric disease, intellectual deficiency, poor motivation, current substance abuse (including illicit drugs and alcohol), or neurological disorders that might interfere with completion of study procedures or hearing problems that may impede effective communication.
  • Study site staff (i.e. participating investigator, sub-investigator, study coordinator, employee of the participating investigator) or family members of site staffs.
  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: NCT01110200

  Show 103 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01110200     History of Changes
Other Study ID Numbers: 113874
Study First Received: April 22, 2010
Results First Received: December 13, 2012
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Hospitalization
Exacerbations of COPD
Chronic Obstructive Pulmonary Disease (COPD)

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Respiratory Tract Diseases
Pathologic Processes
Adrenergic Agonists
Salmeterol
Albuterol
Fluticasone
Fluticasone, salmeterol drug combination
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Tocolytic Agents
Reproductive Control Agents
Anti-Inflammatory Agents
Dermatologic Agents
Anti-Allergic Agents

ClinicalTrials.gov processed this record on August 19, 2014