Effects of Roflumilast in Hospitalized Chronic Obstructive Pulmonary Disease( COPD) on Mortality and Re-hospitalization
Condition: COPD
Intervention: Roflumilast; Placebo
Intervention description: PDE4 inhibitor; Inactive substance.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 68.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: COPD; Emphysema; Roflumilast; readmission

Summary:

      Background: COPD exacerbations add considerably to patients' burden because they: (1) cause
      frequent hospital admissions and relapses or readmissions, (2) contribute directly to the
      death of many patients, either during hospitalization or shortly thereafter, (3) cause
      patients significant stress, prolonged physical discomfort, disability and dramatically
      reduced quality of life, (4) consume the majority of the resources available to manage this
      chronic condition, (5) frequently progress to a severe stage warranting hospitalization
      before any abortive treatment is instituted, and (6) may hasten the progressive loss of lung
      function, a steady decline that is a cardinal feature of COPD itself. Hence, investigations
      of new therapies to treat COPD patients who are hospitalized with a severe exacerbation are
      desperately needed.

      Objective: To test the feasibility of roflumilast to decrease all cause readmission and
      mortality 180 days after hospitalization for acute COPD exacerbation.

      Methods: Parallel-group, prospective, randomized, double blind, placebo-controlled trial of
      roflumilast 500 ug daily vs. placebo in approximately 100 hospitalized AECOPD patients.
      Inclusion Criteria. Primary diagnosis of AECOPD; admission to the hospital <12 hours; patient
      age >40, < 80 years old; cigarette smoking > 10 pack-years. Exclusion Criteria. Prior
      diagnosis or high suspicion for asthma; pulmonary edema, pneumonia, interstitial lung disease
      or significant bronchiectasis; intubated and mechanically ventilated at the time of
      evaluation; active liver disease, or transaminase elevations (> 3xULN); history of heavy
      ethanol use; history of suicidal behavior ≤ 2 years or suicidal ideation ≤ 6 months prior to
      enrollment; pregnant or lactating females. Those on the following excluded medications: P450
      inducers and CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2
      simultaneously
    

Eligibility criteria:

        Inclusion Criteria:

        Primary diagnosis of AECOPD defined as acute increase in dyspnea, sputum volume, and/or
        sputum purulence without other identified cause; admission to the hospital <12 hours;
        patient age >40, < 80 years old; cigarette smoking > 10 pack-years; informed written
        consent.

        Exclusion Criteria:

        Prior diagnosis or high suspicion for asthma based on investigator judgment; pulmonary
        edema, pneumonia, interstitial lung disease or significant bronchiectasis based on
        admission chest x-ray; intubated and mechanically ventilated at the time of evaluation;
        active liver disease, or transaminase elevations (> 3xULN); history of alcoholism or heavy
        ethanol use; history of suicidal behavior ≤ 2 years or suicidal ideation ≤ 6 months prior
        to enrollment; pregnant or lactating females. Those on the following excluded medications:
        P450 inducers (e.g., rifampicin, phenobarbital, carbamazepine, and phenytoin) and CYP3A4
        inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously (e.g.,
        erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine.