Strategy to Improve Adherence of Roflumilast

Adherence to Therapy in COPD Patients Under Dose Escalation of Roflumilast

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).

Study Overview

• Status: Unknown
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Roflumilast escalation dosage; Drug: Roflumilast conventional dosage

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female older than 40 years
2. 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
3. Former smokers or current smokers with at least a 10 pack-year history
4. 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)
5. Chronic bronchitis (cough and sputum production for at least three months within two years)
6. Able to have the signed written informed consent prior to any study-related procedures.

Exclusion Criteria:

1. COPD exacerbation or respiratory infection 4 weeks prior to the baseline visit
2. Known a1-antitrypsin deficiency
3. Need for long-term oxygen therapy
4. Moderate to severe liver impairment (Child-Pugh B or C)
5. Severe immunological diseases (e.g. HIV infection, multiple sclerosis, lupus erythematosus, etc)
6. Severe acute infectious diseases
7. Cancers
8. 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)
9. Latent infections such as tuberculosis, viral hepatitis, herpes viral infection and herpes zoster
10. Subjects with congestive heart failure (NYHA grades 3 and 4)
11. Subjects with a history of depression associated with suicidal ideation or behavior
12. Clinically meaningful bronchiectasis
13. Pregnancy or breast feeding, or Female subjects of childbearing potential unwilling to use effective contraception
14. Patients with known hypersensitivity to Roflumilast or rescue medication and their ingredients
15. Patients with previous Roflumilast therapy within past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Roflumilast escalation dosage; Roflumilast 250 μg qd (4 weeks) →500 μg qd	Drug: Roflumilast escalation dosage; 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; Other Names: Daxas
Experimental: Roflumilast conventional dosage; Roflumilast 500 μg qd	Drug: Roflumilast conventional dosage; Roflumilast 500 μg once daily for 12 weeks; Other Names: Daxas

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Sei Won Lee, MD, Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

Publications and helpful links

General Publications

• Park TS, Kang J, Lee JS, Oh YM, Lee SD, Lee SW. Adherence to roflumilast under dose-escalation strategy in Korean patients with COPD. Int J Chron Obstruct Pulmon Dis. 2019 Apr 16;14:871-879. doi: 10.2147/COPD.S191033. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: December 12, 2013
• First Submitted That Met QC Criteria: December 17, 2013
• First Posted (Estimate): December 23, 2013

Study Record Updates

• Last Update Posted (Estimate): December 23, 2013
• Last Update Submitted That Met QC Criteria: December 17, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: Roflumilast_compliance