Clinical Study for the Effectiveness of Roflumilast Treatment in COPD Greek Patients Based on Standard Clinical Practice. (ARGO)

Clinical Study for the Effectiveness of Roflumilast Treatment in COPD Greek Patients Based on Standard Clinical Practice. An Observational, Non-interventional Multicenter Study.

Preferred pharmacological management for COPD according to the GOLD guidelines are the long-acting anticholinergic LAMAs (Long-Acting / Short-Acting Muscarinic Antagonists), and long-acting β 2-Agonists LABA (Long-acting LABA) / β2-Long Action Fighters) as well as inhaled corticosteroids (ICS) Other drugs that can be used besides long-acting, are short-acting anticholinergics (SAMA) and β2-agonists (SABA), methylxanthines (Aminophylline and Theophylline), mucolytics and phosphodiesterase inhibitors 4 (Phosphorus) of which is roflumilast

Study Overview

• Status: Recruiting
• Conditions: Copd; COPD Exacerbation

Detailed Description

Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor, a non-steroidal, anti-inflammatory active substance intended to target both systemic inflammation and COPD-related lung inflammation. The mechanism of action is the inhibition of PDE4, which is an important enzyme for the metabolism of cyclic adenosine monophosphate (cAMP) found in structural and inflammatory cells, which are important in the pathogenesis of COPD. Roflumilast targets PDE4A, 4B and 4D subtypes with similar activity in the nanomolecular range. The affinity for PDE4C subtypes is 5 to 10 times lower. This mechanism of action and selectivity also apply to roflumilast N-oxide, which is the main active metabolite of roflumilast. Inhibition of PDE4 leads to increased levels of intracellular cAMP and attenuates COPD-related dysfunctions of leukocytes, smooth muscle cells of the airways and lungs, endothelial cells and epithelial cells and epithelial cells. In vitro stimulation of human neutrophils, monocytes, macrophages or lymphocytes, roflumilast and roflumilast N-oxide suppress the release of inflammatory mediators e.g. leukotriene B4, reactive oxygen species, tumor necrosis factor α, interferon γ and granzyme B.

In patients with COPD, roflumilast reduced neutrophils in the sputum. In addition, it mitigated the influx of neutrophils and eosinophils into the airways of healthy volunteers following endotoxin challenge. Studies using roflumilast have shown that there has been a statistically significant and clinically significant reduction in exacerbations in COPD patients. Depending on the study, a reduction ranging from 15% -37% was observed. In 2 placebo-controlled 12-month roflumilast studies, where 50% of patients were on maintenance therapy with a LABA, the reduction in exacerbations was 17% (P <0.001) (12). Also, in 2 studies of roflumilast for 6 months, controlled with placebo, the reduction of exacerbations when taken with salmeterol was 37%, P = 0.0315 (post-hoc analysis) or with Tiotropium 23%, P = 0.196.

The drug of the present study is Damirast 500 mg of which the active substance is roflumilast. It is a potent selective PDE4 inhibitor with multiple anti-inflammatory actions. Improves pulmonary function (48-55mL), reduces exacerbations (15-37%)and prolongs the time to the first exacerbation (up to 40%).

Damirast is indicated for the maintenance treatment of severe chronic obstructive pulmonary disease (COPD) in addition to bronchodilator therapy, LABA / LAMA and / or inhaled corticosteroids.

Damirast is an innovative anti-inflammatory treatment specifically designed for COPD patients with chronic cough and sputum. The anti-inflammatory action of Damirast reduces the incidence of exacerbations, while it also actively contributes to the improvement of the patient's lung function, making it the appropriate medication for the long-term treatment of COPD. In addition, once daily oral administration is expected to play a key role in patient compliance, as it offers the added benefit of systematic availability and easy access. Damirast can thus reach even the smallest and most distant bronchi and pulmonary alveoli, which are often blocked by mucus, making it difficult to exchange gases and prevent the absorption of inhaled drugs.

• Study Type: Observational
• Enrollment (Estimated): 750

Contacts and Locations

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece
      • Recruiting
      • Sotiria Hospital
      • Contact: Katerina Papataxiarchou; Phone Number: +306934088660; Email: k.papataxiarchou@elpen.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with COPD which is now one of the top three causes of death worldwide. In Greece there are about 700,000 patients with COPD (prevalence 10.6%) and similar is the global prevalence (9-10%) of the disease for adults over 40 years.

Preferred pharmacological management for COPD according to the GOLD guidelines are the long-acting anticholinergic LAMAs (Long-Acting / Short-Acting Muscarinic Antagonists), and long-acting β 2-Agonists LABA (Long-acting LABA) / β2-Long Action Fighters) as well as inhaled corticosteroids (ICS).

Other drugs that can be used besides long-acting, are short-acting anticholinergics (SAMA) and β2-agonists (SABA), methylxanthines (Aminophylline and Theophylline), mucolytics and phosphodiesterase inhibitors 4 (Phosphorus) of which is roflumilast.

Description

Inclusion criteria

1. Adult patients indicated for maintenance treatment of severe COPD associated with chronic bronchitis with a history of frequent exacerbations in addition to bronchodilator / ICS therapy.
2. Consent and compliance with the therapies and study procedures. Exclusion criteria According to the contraindications of the SPC of the product. Patients should not take theophylline.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in CCQ	(Clinical COPD Questionnaire) changes in 3-6-9-12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in mMRC	(Modified Medical Research Council) changes in 3-6-9-12 months	12 months
change in CAT	(COPD Assessment Test) changes in 3-6-9-12 months	12 months

Collaborators and Investigators

• Sponsor: Elpen Pharmaceutical Co. Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: June 16, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Lung Diseases, Obstructive; Chronic Disease; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 2022-ROFDAM-EL-161

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No