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

Assiut University

Status and phase: Unknown; Early Phase 1

Conditions: Bronchiectasis

Treatments: Drug: Roflumilast

Study type: Interventional

Funder types: Other

Identifiers

NCT04090294

Roflumilast in bronchiectasis

Details and patient eligibility

About

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

Full description

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.

Enrollment: 35 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Roflumilast -non roflumilast

Experimental group

Description:

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.

Treatment:

Drug: Roflumilast