Strategy to Improve Adherence of Roflumilast

Study Overview
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Brief Summary
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Main adverse events of Roflumilast are weight loss, loss of appetite, insomnia, headache, diarrhea, vomiting, and nausea. Although the majority of these adverse reactions were mild or moderate. They occurred mainly at the beginning of therapy and mostly resolved with continued treatment around for two weeks according to experiences of clinicians. These adverse events occur more often in Roflumilast 500 μg than 250 μg, having negative impact on compliance of patients at the early stage of treatments. Thus, investigators aim to compare the drop-out rates between the usual dosage (Roflumilast 500 μg once daily) and the dose escalation (Roflumilast 250 μg once daily for 4 weeks and then escalating dose of 500 μg once daily).

Official Title
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Adherence to Therapy in COPD Patients Under Dose Escalation of Roflumilast

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Roflumilast escalation dosage
* Drug: Roflumilast conventional dosage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female older than 40 years Clinical diagnosis of COPD (confirmed with a post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC] ratio ≤70%) at least 4 weeks prior to the study and post-bronchodilator FEV1 is 50% or less than the predicted value Former smokers or current smokers with at least a 10 pack-year history A history of exacerbation (scheduled/unscheduled visits to primary care physicians, specialists or allied healthcare professionals, or emergency room, or hospitalization due to purulent sputum or increased sputum, or increased dyspnea) in the previous year (at least one) Chronic bronchitis (cough and sputum production for at least three months within two years) Able to have the signed written informed consent prior to any study-related procedures. Exclusion Criteria: COPD exacerbation or respiratory infection 4 weeks prior to the baseline visit Known a1-antitrypsin deficiency Need for long-term oxygen therapy Moderate to severe liver impairment (Child-Pugh B or C) Severe immunological diseases (e.g. HIV infection, multiple sclerosis, lupus erythematosus, etc) Severe acute infectious diseases Cancers Subjects being treated with immunosuppressive medicinal products (i.e.: methotrexate, azathioprine, infliximab, etanercept, or oral corticosteroids to be taken long-term) except short-term systemic corticosteroids) Latent infections such as tuberculosis, viral hepatitis, herpes viral infection and herpes zoster Subjects with congestive heart failure (NYHA grades 3 and 4) Subjects with a history of depression associated with suicidal ideation or behavior Clinically meaningful bronchiectasis Pregnancy or breast feeding, or Female subjects of childbearing potential unwilling to use effective contraception Patients with known hypersensitivity to Roflumilast or rescue medication and their ingredients Patients with previous Roflumilast therapy within past 3 months

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roflumilast escalation dosage<br>Roflumilast 250 μg qd (4 weeks) →500 μg qd | Drug: Roflumilast escalation dosage<br>* This is a randomized, prospective, open label, comparative study to assess whether the administration of roflumilast by dose escalation varies the incidence of discontinuations due to adverse events when compared with the usual dosage in severe and very severe COPD patients. Roflumilast 250 μg once daily for 4 weeks and then increased dose of Roflumilast 500 μg once daily for 12 weeks<br>* Other names: Daxas;|
| Experimental: Roflumilast conventional dosage<br>Roflumilast 500 μg qd | Drug: Roflumilast conventional dosage<br>* Roflumilast 500 μg once daily for 12 weeks<br>* Other names: Daxas;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| medication(Roflumilas) history taking | In every follow-up, patients will be asked about their medication history. The patients will count the rest of the Roflumilast that they are going to take in the future. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory test : Hematology, Biochemistry, and Urinalysis | •Laboratory test : Hematology, Biochemistry, and Urinalysis | 16 weeks | 
| Urine pregnancy test | •Urine pregnancy test | 16 weeks | 
| Chest X-ray Test | •Chest X-ray Test | 16 weeks | 
| ECG Test | •ECG Test | 16 weeks | 
| Lung Function Test | •Lung Function Test | 16 weeks | 
| QoL Questionnaire (CAT score) | •QoL Questionnaire (CAT score) | 16 weeks | 
| Other tests (HBsAg, HCV, HIV) | •Other tests (HBsAg, HCV, HIV) | 16 weeks |