Assessment of Early Outcomes of Roflumilast in Patients With Non Cystic Fibrosis Bronchiectasis

Study Overview
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Brief Summary
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Aim of the work Assessment of early outcome of using Roflumilast in patients with bronchiectasis regarding: Severity of symptoms Frequency of exacerbations Change in pulmonary function Systemic inflammation

Detailed Description
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Bronchiectasis is defined by the presence of permanent and abnormal dilation of the bronchi. This usually occurs in the context of chronic airway infection causing inflammation. The main clinical manifestation is a productive cough. Bronchiectasis is currently nearly always diagnosed using high-resolution computed tomography (HRCT) scanning. The main diagnostic features are: 1) internal diameter of a bronchus is wider than its adjacent pulmonary artery; 2) failure of the bronchi to taper; and 3) visualization of bronchi in the outer 1-2 cm of the lung fields. From a series of benzamide derivatives, roflumilast (3-cyclo-propylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) was identified as a potent and selective PDE4 inhibitor. It inhibits PDE4 activity from human neutrophils. PDE4 inhibitors were demonstrated to inhibit inflammatory cytokine and mediator release from inflammatory cells. In addition, it inhibits neutrophil chemotaxis or migratory activity. Lastly, PDE4 inhibitor promotes apoptosis of these cells . Studies have demonstrated the efficacy of roflumilast in patients with both asthma and COPD, where roflumilast improved lung function and reduced exacerbation rates. Bronchiectasis is a chronic destructive lung disease, which is characterised by persistent bacterial colonization, bronchial inflammation, reduced mucociliaryclearance, and in some patients progressive tissue damage. There is evidence of an associated influx of neutrophils into the lungs of these patients , resulting in the expectoration of large volumes of purulent sputum containing neutrophils and their products, so In patients with bronchiectasis, there is also neutrophilic inflammation as in COPD. The PDE4 inhibitor, roflumilast, was evaluated in short term clinical trial of non-cystic fibrosis bronchiectasis. It has been shown symptomatic improvement from baseline Park J. found that 16 weeks Roflumilast treatment in patients with non cystic fibrosis bronchiectasis significantly reduce CAT score and improve the symptoms of non-CF bronchiectasis.

Official Title
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Assessment of Early Outcomes of Roflumilast in Patients With Non Cystic Fibrosis Bronchiectasis

Conditions
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Bronchiectasis

Intervention / Treatment
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* Drug: Roflumilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or above, male or female. Non / Ex-smokers. Confirmed diagnosis of bronchiectasis based on high-resolution computed tomography scan. Significant sputum production (≥ 10 ml per day). Exclusion Criteria: Non-stable patients who need ICU admission /mechanical ventilation. Active smokers. Moderate to severe liver impairment (Child-Pugh B or C) and/or sever renal impairment (c. clearance less than 30ml/min). Known psychiatric illness Concomitant use of strong cytochrome P450 inducers (e.g. rifampicin) Patients who are hypersensitive to roflumilast. Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Interventional Model Description: 35 patients will receive roflumilast for three months and improvement regarding performance , frequency of exacerbation and pulmonary function test will be assessed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roflumilast -non roflumilast<br>35 patients will receive Roflumilast for three months and improvement regarding dyspnea scales , Pulmonary function Test , Six minutes walking test and bronchectasis severity index (FACED) score pre and post therapy will be assessed. patients will receive Roflumilast 500 Mcg. Tablet Once daily for Three months and then base line assessment will be repeated to evaluate improvement. | Drug: Roflumilast<br>* Roflumilast is a phosphodiesterase (PDE) type 4 inhibitor will be prescribed for three month for the study group. the patients will then be assessed for improvement regarding exacerbation frequency , performance and pulmonary function test. patients will receive Roflumilast 500 Mcg. Tablet once daily for three months<br>* Other names: phosphodiestrase 4 inhibitor (PDE4);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of efficacy of Roflumlilast regarding control of patients with non cystic fibrosis bronchiectasis | Assessment of efficacy of Roflumilast on severity of symptoms in patients with bronchiectasis. Frequency of Exacerbation in the three months assessment and need of hospitalization will be the main parameter for efficacy of the new treatment described as number/ 3 months | 3months . outcomes will be evaluated after 1month and at the end of the study (3months). | 
| Assessment of efficacy of roflumlilast in change of performance in patients with non cystic fibrosis bronchiectasis | Assessment of efficacy of roflumilast on change dyspnea scale namely mMRCP evaluated at the start of the study and after 1 month and 3 months | 3months . outcomes will be evaluated after 1month and at the end of the study (3months). | 
| Assessment of efficacy of roflumlilast on change in Pulmonary function in patients with non cystic fibrosis bronchiectasis | Assessment of efficacy of roflumilast on change in pulmonary function test in patients with bronchiectasis regarding : change in FEV1 by liter per second | 3months . outcomes will be evaluated after 1month and at the end of the study (3months). | 
| Assessment of efficacy of roflumlilast on change of symptoms in patients with non cystic fibrosis bronchiectasis | Assessment of efficacy of roflumlilast on severity of symptoms in patients with bronchiactasis evaluated by bronchectasis severity index (FACED) score. | 3months . outcomes will be evaluated after 1month and at the end of the study (3months). | 
| Assessment of efficancy of roflumlilast on change in systemic inflammation in patients with non cystic fibrosis bronchiectasis | Assessment of efficacy of roflumlilast on systemic inflammation in patients with bronchiectasis regarding CRP by mg per L | 3months . outcomes will be evaluated after 1 month and at the end of the study (3 months). |