Effect of Roflumilast on Quality of Life, Lung Function and Mucus Properties in Patients With Bronchiectasis

NCT ID: NCT03988816

Last Updated: 2020-01-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-06
• Study Completion Date: 2020-12-31

Brief Summary

Although relatively common, bronchiectasis is considered an orphan disease as there is little evidence for adequate treatment, most of the therapeutic options are extrapolated from studies with patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Inhaled bronchodilators and corticosteroids should be used as a therapeutic test and maintained if there is improvement of symptoms or lung function. There is no evidence to justify the use of mucolytic agents for these patients. The treatment with greater evidence is the use of macrolides, especially azithromycin. A meta-analysis published in 2014 showed that there was a reduction in the number of exacerbations, an improvement in the quality of life and a reduction in the decrease in FEV1. However, studies have shown conflicting results regarding quality of life and pulmonary function.

Roflumilast is a phosphodiesterase-4 inhibitor with an anti-inflammatory effect in vitro and in vivo due to the inhibition of cyclic adenosine monopostat breakdown (cAMP) to its inactive phosphodiesterase form. As this enzyme is expressed in high concentrations in leukocytes and other inflammatory cells responsible for the pathogenesis of pulmonary diseases such as COPD, it has been studied and used for this disease. COPD is characterized by a chronic inflammatory process of the airways, predominantly neutrophils and high levels of proinflammatory cytokines related to this cell, such as interleukin-8, neutrophil elastase, tumor necrosis factor (TNF) alpha and E-selectin. The REACT study showed that roflumilast prevents moderate and severe infectious exacerbations in addition to improved lung function in patients with COPD who continue to exacerbate despite the use of combined bronchodilator and inhaled corticosteroid therapy.

Since bronchiectasis and COPD are chronic inflammatory diseases, they present similar inflammatory processes, with neutrophil as the main inflammatory cell, it is expected that the use of roflumilast also has an anti-inflammatory effect in bronchiectasis. In addition, since bronchiectasis is a disease with poor evidence for pharmacological treatment, it is necessary to search for new therapeutic possibilities.

Conditions

Bronchiectasis Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Roflumilast

Roflumilast tablets will be supplied at a concentration of 500 mcg. Each tablet contains 500mcg of the active ingredient in addition to the excipients: lactose monohydrate, corn starch, povidone and magnesium stearate. The coating contains hypromellose, macrogol, titanium dioxide, yellow iron oxide. Patients should take 1 tablet once daily, before, during or after meals, at the same time each day.

Group Type: EXPERIMENTAL

Roflumilast

Intervention Type: DRUG

500Mcg Tab, once daily

Placebo (control)

Roflumilast placebo-containing tablets will look similar to active roflumilast tablets and will be supplied to patients in packs identical to those of the active drug.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

once daily

Interventions

Roflumilast

500Mcg Tab, once daily

Intervention Type: DRUG

Placebo oral tablet

once daily

Intervention Type: DRUG

Other Intervention Names

Daxas; Placebo

Eligibility Criteria

Inclusion Criteria

• Age > 18 years;
• Diagnosis of bronchiectasis by chest tomography;
• FEV1 <60% of predicted;
• History of chronic bronchitis (chronic cough and sputum for at least 3 months in the last 2 years);
• 2 or more infectious exacerbations in the last year (defined as worsening of cough and / or dyspnoea and / or decreased general condition, increased quantity and purulence of sputum that required systemic antibiotic use (oral or intravenous).

Exclusion Criteria

• Hemoptysis in the last 6 months (significance at the discretion of the investigator);
• Current or prior smoking if > 10 pack-years;
• FEV1 < 30% of predicted;
• Known allergy to roflumilast;
• Pulmonary exacerbation present or occurring in the last 4 weeks;
• Child B or C cirrhosis;
• Active cancer (except basal cell carcinoma);
• Severe heart failure;
• Depression associated with suicidal ideation;
• Pregnancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

University of Sao Paulo General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rodrigo A Athanazio, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical Assistant

Locations

Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Rodrigo A Athanazio, MD, PhD

Role: CONTACT

rathanazio@yahoo.com.br

+55 11 2661-5000 ext. 5685

Facility Contacts

Rodrigo A Athanazio, MD, PhD

Role: primary

rathanazio@yahoo.com.br

+55 11 2661-5000 ext. 5685

Blenda Nunes, MD

Role: backup

blendaendlich@gmail.com

+55 11 2661-5000 ext. 5685

References

Fjaellegaard K, Sin MD, Browatzki A, Ulrik CS. Antibiotic therapy for stable non-CF bronchiectasis in adults - A systematic review. Chron Respir Dis. 2017 May;14(2):174-186. doi: 10.1177/1479972316661923. Epub 2016 Aug 9.

Reference Type: BACKGROUND

PMID: 27507832 (View on PubMed)

Quint JK, Millett ER, Joshi M, Navaratnam V, Thomas SL, Hurst JR, Smeeth L, Brown JS. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. Eur Respir J. 2016 Jan;47(1):186-93. doi: 10.1183/13993003.01033-2015. Epub 2015 Nov 5.

Reference Type: BACKGROUND

PMID: 26541539 (View on PubMed)

McShane PJ, Naureckas ET, Tino G, Strek ME. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2013 Sep 15;188(6):647-56. doi: 10.1164/rccm.201303-0411CI.

Reference Type: BACKGROUND

PMID: 23898922 (View on PubMed)

Beghe B, Rabe KF, Fabbri LM. Phosphodiesterase-4 inhibitor therapy for lung diseases. Am J Respir Crit Care Med. 2013 Aug 1;188(3):271-8. doi: 10.1164/rccm.201301-0021PP.

Reference Type: BACKGROUND

PMID: 23656508 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17573446 (View on PubMed)

Other Identifiers

2018/17035-5

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SDC 4706/18/057

Identifier Type: -

Identifier Source: org_study_id