TNF-alpha Antagonists for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00789997
First received: November 12, 2008
Last updated: October 20, 2011
Last verified: October 2011
  Purpose

The purpose of this study is to determine whether treatment with antibiotics plus a TNFalpha antagonist will provide more effective treatment for acute COPD exacerbation compared to the current standard treatment of antibiotics plus prednisone.


Condition Intervention Phase
COPD Exacerbation
Drug: Etanercept + Levofloxacin + placebo prednisone capsules
Drug: Prednisone + Levofloxacin + placebo Etanercept subcutaneous injections
Phase 2
Phase 3

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: TNF-alpha Antagonists for Acute Exacerbations of COPD: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Change in lung function (FEV1) [ Time Frame: Day 0 to Day 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to treatment failure assessed within a 90 day period, Disease specific quality of life, Improvement in subjective dyspnea score, Safety- incidence of short- and long-term adverse events, [ Time Frame: Day 0 to Day 90 ] [ Designated as safety issue: No ]

Enrollment: 81
Study Start Date: November 2008
Study Completion Date: October 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etanercept Drug: Etanercept + Levofloxacin + placebo prednisone capsules
Levofloxacin 750 mg daily for 10 days + etanercept 50 mg subcutaneous given on the day of randomization and one week later + placebo prednisone capsule, 1 daily for 10 days.
Active Comparator: Prednisone Drug: Prednisone + Levofloxacin + placebo Etanercept subcutaneous injections
Levofloxacin 750 mg daily for 10 days + prednisone 40 mg daily for 10 days + placebo subcutaneous injections given on day of randomization and one week later.

Detailed Description:

Acute exacerbations of COPD (AECOPD)are usually treated with steroids and antibiotics. Currently this conventional therapy has significant side effects including osteoporosis, cataracts,and suppression of the immune system. Studies have suggested that up to 24% of inpatients and 27% of outpatients fail this treatment by 4 weeks. During an acute exacerbation of COPD, the inflammatory process increases. Studies have shown the TNF-alpha cytokines appears to play a major role. Etanercept is a TNF alpha inhibitor. It inactivates TNF alpha cytokines by blocking their interaction with their cellular receptors. This study will compare the treatment of acute exacerbations of COPD with: 1) Levofloxacin 750 mg daily for 10 days + prednisone 40 mg daily for 10 days, or 2) Levofloxacin 750 mg daily for 10 days + etanercept 50 mg subcutaneous given on the day of randomization and one week later. Patients randomized to group 1 (the control group) will receive placebo subcutaneous injections, and patients randomized to group 2 (the experimental group) will receive placebo prednisone capsules.

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Both inpatients and outpatients with acute COPD exacerbation will be selected for randomization. Patients will be considered to fulfill the diagnosis of AECOPD if they meet the following 5 criteria:

  1. Patients must have had a previous diagnosis of chronic bronchitis, emphysema or COPD established by a physician.
  2. Patients must have evidence of airflow obstruction on presentation, defined as an FEV1 equal to or less than 70% of predicted and a FEV1 / FVC ratio less 70%.
  3. Patients must be > 35 years old.
  4. Patients must have a minimum history of 10 pack years smoking.
  5. Patients must be experiencing an acute exacerbation of COPD and must meet at least two of the following three clinical criteria for acute COPD exacerbation as defined by Anthonisen:

    • increased chronic baseline dyspnea,
    • increased sputum volume or increased sputum purulence

The above complaints had to have necessitated the emergency department or physician visit.

Exclusion Criteria:

  1. Respiratory failure necessitating admission to an intensive care unit or necessitating use of mechanical invasive or non-invasive (BIPAP) mechanical ventilation.
  2. Physician diagnosed asthma.
  3. Any patient who has used oral or injectable corticosteroids during the month preceding trial entry will be excluded,except for patients who have received a single dose of oral or injectable steroids (up to the equivalent of 125 mg of methylprednisolone) in the emergency department prior to randomization. (Note that standard clinical practice in emergency departments is to treat these patients with oral or intravenous steroids on presentation to the ED. Since it will be functionally impossible to randomize patients prior to initial ED treatment we will allow randomization of patients who have been given a single dose of steroid in the ED).
  4. History of chronic lung disease other than COPD. Patients with a history of bronchiectasis, cystic fibrosis, lung cancer and interstitial lung disease.
  5. Pneumonia or congestive heart failure or suspected malignancy on CXR prior to randomization.
  6. Patients with a history of infection, or suspected current infection, with mycobacteria tuberculosis, non-tuberculous mycobacteria, or fungal infection.
  7. Patients not able to perform an FEV1 assessment.
  8. Patients with known adverse reaction or intolerance to systemic steroids or TNF-alpha antagonists.
  9. Patients with a history of multiple sclerosis or demyelinating disease (etanercept is contraindicated in these patients).
  10. Inability to provide informed consent or comply with the study protocol due to cognitive impairment, language barrier, or distance > 100 kilometres from the study centre.
  11. Patients with a history of HIV or other immuno-compromising diseases.
  12. Patients with a known malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that was treated with no evidence of recurrence).
  13. Patients who have serum WBC count < 3,000 or platelet count < 100,000 at time of randomization.
  14. Patients who are pregnant or nursing will be excluded. Females of child-bearing age will be required to have a negative serum or urine pregnancy test before randomization.
  15. Patients with suspected sepsis- ie. those with temperature > 38.5 degrees or serum WBC> 20 000 will be excluded.
  16. Patients who have a history or active infection with viral Hepatitis B or Hepatitis C.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00789997

Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
Principal Investigator: Shawn Aaron, MD, MSc Ottawa Hospital Research Institute
  More Information

No publications provided by Ottawa Hospital Research Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT00789997     History of Changes
Other Study ID Numbers: 2007791-01H
Study First Received: November 12, 2008
Last Updated: October 20, 2011
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:
COPD Exacerbation
Etanercept
TNF alpha
Randomized

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Ofloxacin
Prednisone
TNFR-Fc fusion protein
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antirheumatic Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 20, 2014