Brief Title
Inhaled A1AT in Adult Stable Bronchiectasis
Official Title
Effects of Inhaled Alpha-1-anti-trypsin on Proteolytic Activity in BAL of Bronchiectasis Patients With Chronic Bronchial Expectoration
Brief Summary
Aim: to investigate the influence of alpha1-antitrypsin (A1-AT) nebulization on levels of A1-AT in BAL and plasma in patients with stable bronchiectasis. Method: single-blind placebo-controlled randomised clinical trial. 19 stable bronchiectasis patients with chronic bronchial infection and 10 control patients (without bronchiectasis) underwent a bronchoscopy in order to assess levels and inhibitory capacity of A1AT and neutrophilic elastase. Afterwards, the 19 bronchiectasis patients were randomly allocated to receive inhaled A1AT 250mg diluted in 10ml 0.9% saline solution once a day for a month (Group A, n: 10) or placebo (10ml 0.9% saline solution; group B, n: 9). A new BAL was performed in both groups (A and B) 24 hours after the end of treatment (1month) to re-analyze A1AT and NE.
Detailed Description
Effects of inhaled alpha-1-anti-trypsin in bronchiectasis patients with chronic bronchial infection. Introduction: one of the main features of bronchiectasis is chronic and deregulated neutrophilic bronchial inflammation. Excessive neutrophilic elastase (NE) activity has been widely described as part of the characteristic imbalance between proteases and anti-proteolytic enzymes that characterizes airways inflammation and progressive lung damage in bronchiectasis. Alpha-1-antitrypsin (A1AT) is a protease inhibitor involved in protecting lung tissue from enzymes of inflammatory cells, including neutrophilic elastase, and its concentration rises in case of acute and chronic inflammation. Its reduction or absence is associated with the development of a specific kind of emphysema in case of exposure to tobacco smoking. Moreover it is likely that its levels could be reduced in bronchiectasis as a consequence of chronic bronchial infection and inflammatory deregulation. Aims: 1. concentrations of total and free NE, NE inhibitory capacity and A1AT levels were investigated in broncho-alveolar lavage (BAL) of bronchiectasis patients with chronic airways infection in stable conditions in comparison with a control group (patients without bronchiectasis) 2. The effects of inhaled A1AT (Prolastin) on BAL concentration of total and free NE and A1AT and inhibitory capacity of NE were assessed after one month of treatment in patients with bronchiectasis and chronic bronchial infection (placebo controlled trial) Study design: simple blind placebo-controlled randomized clinical trial Methods: 19 patients with stable non cystic fibrosis bronchiectasis and chronic bronchial infection and 10 patients without bronchiectasis (control group) underwent a bronchoscopy to perform BAL analysis. The 19 bronchiectasis patients were randomly allocated to receive inhaled A1AT 250mg diluted in 10ml 0.9% saline solution once a day for a month (Group A, n: 10) or placebo (10ml 0.9% saline solution; group B, n: 9). A new BAL was performed in both groups (A and B) 24 hours after the end of treatment (1month) to re-analyze A1AT and NE. Clinical, microbiological, biochemical, functional and radiological characteristics of bronchiectasis and potential side effects of treatment on both arms were also recorded before (baseline), at 7, 15, 30 days of treatment and at 1 and 2 months follow-up visits after the end of treatment. The trial was approved by Spanish Ministry of Health (Trial nº 95/256) and local Ethics Committee (AC(HG) 44/95) and all patients signed written consent.
Study Type
Interventional
Primary Outcome
Changes from baseline BAL levels of A1AT
Secondary Outcome
Changes from baseline neutrophil elastase in BAL
Condition
Bronchiectasis Adult
Intervention
Group A
Study Arms / Comparison Groups
group A
Description: 10 patients randomly allocated received nebulised alpha1-antitrypsin 250mg (diluted in 10ml injectable solution) once a day during 1 month. Intervention: nebulised alpha1-antitrypsin 250mg (diluted in 10ml injectable solution) once a day during 1 month
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
June 1, 1996
Completion Date
September 7, 1999
Primary Completion Date
September 7, 1999
Eligibility Criteria
Inclusion Criteria: - Stable clinical conditions (no use of systemic antibiotic or steroid treatment in the last month) - diagnosis of bronchiectasis bt CT scan - chronic purulent or mucopurulent expectoration (daily sputum expectoration in the last 6 months or more) Exclusion Criteria: - Cystic fibrosis - interstitial lung disease as cause of bronchiectasis
Gender
All
Ages
18 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
Javier De Gracia, MD, PhD, ,
Administrative Informations
NCT ID
NCT03383939
Organization ID
AC(HG) 44/95
Responsible Party
Sponsor
Study Sponsor
Hospital Universitari Vall d'Hebron Research Institute
Collaborators
Bayer
Study Sponsor
Javier De Gracia, MD, PhD, Principal Investigator, Servei de Pneumologia, Vall D'Hebron Hospital
Verification Date
December 2017