A Placebo-controlled Trial of Daliresp on Chronic Obstructive Pulmonary Disease (COPD)

A Placebo-controlled Trial of Roflumilast (Daliresp) on Markers of Inflammation in Chronic Obstructive Pulmonary Disease (COPD)

The purpose of the study is to propose that roflumilast is associated with meaningful reductions in biomarkers of pulmonary inflammation and sputum neutrophilia, including confirmation of previously described results, and correlate these findings with improvement in pulmonary function, sputum scores, and quality of life in stable moderate to severe COPD. The investigators aim to demonstrate this regardless of concomitant medication use, including inhaled corticosteroids. Additionally, the investigators hope to provide a mechanistic pathway by which these effects occur.

Inclusion Criteria:

1. Male and female subjects, > 40 years of age

2. Clinical diagnosis of moderate to severe COPD as defined by the GOLD criteria:

   Post-bronchodilator FEV1/FVC < 70% Post-bronchodilator FEV1 < 70% predicted

3. Cigarette consumption of 10 pack-years or more. Patients may be active smokers.

4. The presence of chronic cough and sputum production

5. Willingness to make return visits and telephone availability for the study duration

Exclusion Criteria:

1. A diagnosis of asthma as established by the study investigator on the basis of the recent American Thoracic Society/European Respiratory Society guidelines

2. Clinically significant bronchiectasis

3. Oxygen use >12 hours/day

4. Known sensitivity to roflumilast

5. Use of other methylxanthines within 1 month (theophylline)

6. Changes to current maintenance COPD therapy within one month

7. Pregnancy

8. An acute illness requiring antibiotics and/or corticosteroids within the month prior to enrolment.

9. Immunosuppression

   1. HIV
   2. Solid organ transplant
   3. Active malignancy
   4. Systemic corticosteroid use ≥ prednisone 20mg / day
   5. Other immunosuppressants

10. Terminal illness defined as anticipated survival <12 months

11. Severe comorbidities including uncontrolled angina, congestive heart failure, end-stage renal disease, liver failure, or other conditions that would preclude the patient from safely completing the required tests or the study.

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