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

Bronchiectasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04090294
• Other study ID #: Roflumilast in bronchiectasis
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: October 1, 2019
• Est. completion date: November 2020

Study information

• Verified date: September 2019
• Source: Assiut University
• Contact: Maha Ahmed Okasha, Resident
• Phone: 01002660421
• Email: maha.ahmed201388[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 35
• Est. completion date: November 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Drug:
• Roflumilast
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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (4)

Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. Review. — View Citation

Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbröker D, Bethke TD, Hiemstra PS, Rabe KF. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax. 2007 Dec;62(12):1081-7. Epub 2007 Jun 15. — View Citation

Sousa LP, Lopes F, Silva DM, Tavares LP, Vieira AT, Rezende BM, Carmo AF, Russo RC, Garcia CC, Bonjardim CA, Alessandri AL, Rossi AG, Pinho V, Teixeira MM. PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3K/Akt-dependent and NF-kappaB-independent manner. J Leukoc Biol. 2010 May;87(5):895-904. doi: 10.1189/jlb.0809540. Epub 2010 Jan 26. — View Citation

van Schalkwyk E, Strydom K, Williams Z, Venter L, Leichtl S, Schmid-Wirlitsch C, Bredenbröker D, Bardin PG. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions. J Allergy Clin Immunol. 2005 Aug;116(2):292-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).

External Links

•   2. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW. Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respir Med. 2006;100:2183-2189. [PubMed] [Google Scholar]
•   The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease.Pulm Pharmacol Ther 2010;23:235-56. 10.1016/j.pupt.201