Clinical trial NCT04090294: Assessment of Early Outcomes of Roflumilast in Patients With Non Cystic Fibrosis Bronchiectasis
Official title: Assessment of Early Outcomes of Roflumilast in Patients With Non Cystic Fibrosis Bronchiectasis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Bronchiectasis
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2019-09-16
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 35 patients will receive roflumilast for three months and improvement regarding performance , frequency of exacerbation and pulmonary function test will be assessed.
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Assessment of efficacy of Roflumlilast regarding control of patients with non cystic fibrosis bronchiectasis
timeFrame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
measure: Assessment of efficacy of roflumlilast in change of performance in patients with non cystic fibrosis bronchiectasis
timeFrame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
measure: Assessment of efficacy of roflumlilast on change in Pulmonary function in patients with non cystic fibrosis bronchiectasis
timeFrame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
measure: Assessment of efficacy of roflumlilast on change of symptoms in patients with non cystic fibrosis bronchiectasis
timeFrame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
measure: Assessment of efficancy of roflumlilast on change in systemic inflammation in patients with non cystic fibrosis bronchiectasis
timeFrame: 3months . outcomes will be evaluated after 1 month and at the end of the study (3 months).
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Assuit University - Assuit - Egypt
name: Ahmad Shaddad, Lecturer
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available.
citation: Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbroker 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. doi: 10.1136/thx.2006.075937. Epub 2007 Jun 15.
citation: van Schalkwyk E, Strydom K, Williams Z, Venter L, Leichtl S, Schmid-Wirlitsch C, Bredenbroker 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. doi: 10.1016/j.jaci.2005.04.023.