TNF-alpha Antagonists for AECOPD: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00789997
• Date of registration: 12/11/2008
• Prospective Registration: No
• Primary sponsor: Ottawa Hospital Research Institute
• Public title: TNF-alpha Antagonists for AECOPD: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial
• Scientific title: TNF-alpha Antagonists for Acute Exacerbations of COPD: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial
• Date of first enrolment: November 2008
• Target sample size: 81
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00789997
• Study type: Interventional
• Phase: Phase 2/Phase 3

Countries of recruitment

Canada

Contacts

• Name: Shawn Aaron, MD, MSc
• Affiliation: Ottawa Hospital Research Institute

Key inclusion & exclusion 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
forced expiratory volume at one second (FEV1) equal to or less than 70% of predicted
and a FEV1 / forced vital capacity (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 chest x-ray (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 white blood cell count (WBC) < 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.



Age minimum: 35 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

COPD Exacerbation

Intervention(s)

Drug: Etanercept

Drug: levofloxacin

Drug: Prednisone

Primary Outcome(s)

Change in Lung Function (Forced Expiratory Volume in 1 Second (FEV1) [Time Frame: Day 0 to Day 14]

Secondary Outcome(s)

Number of Participants With Treatment Failure by 90 Days Assignment [Time Frame: Day 0 to Day 90]

Secondary ID(s)

2007791-01H

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/04/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00789997