Inhaled A1AT in Adult Stable Bronchiectasis

NCT ID: NCT03383939

Last Updated: 2017-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-06-01

Study Completion Date

1999-09-07

Brief Summary

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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

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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.

Conditions

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Bronchiectasis Adult

Keywords

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bronchiectasis alpha1-antitrypsin neutrophilic elastase

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

2 parallel groups of patients with bronchictasis were investigated: 1 receiving inhaled prolastina and 1 receiving placebo (saline solution) all bronchiectasis patients were initially compared with 10 control patients with no bronchiectasis
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

SINGLE

Investigators

Study Groups

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group A

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

Group Type EXPERIMENTAL

Group A

Intervention Type DRUG

one nebulization with 250mg alpha-1-antitrypsine diluted in 10ml injectable solution once a day during 1 month. A CR-60 high flow compressor and Ventstream nebulizer were used for nebulization.

group B

9 patients randomly allocated received 10ml 0.9%NaCl saline solution nebulised once daily during 1 month.

intervention: 10ml 0.9% Sodium Chloride saline solution nebulised once daily during 1 month.

Group Type PLACEBO_COMPARATOR

Group B

Intervention Type DRUG

10ml of 0.9% NaCl saline solution nebulised once daily for 1 month. A CR-60 high flow compressor and Ventstream nebulizer were used for nebulization.

Control

10 patients without bronchiectasis were initially compared wiht bronchiectasis patients (group A + B) to define baseline levels of A1-AT and neutrophil elastase in BAL

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Group A

one nebulization with 250mg alpha-1-antitrypsine diluted in 10ml injectable solution once a day during 1 month. A CR-60 high flow compressor and Ventstream nebulizer were used for nebulization.

Intervention Type DRUG

Group B

10ml of 0.9% NaCl saline solution nebulised once daily for 1 month. A CR-60 high flow compressor and Ventstream nebulizer were used for nebulization.

Intervention Type DRUG

Other Intervention Names

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inhaled Prolastin (nebulized alpha1-antitrypsin) placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

Sociedad Española de Neumología y Cirugía Torácica

OTHER

Sponsor Role collaborator

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role collaborator

Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Javier De Gracia, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Servei de Pneumologia, Vall D'Hebron Hospital

Other Identifiers

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AC(HG) 44/95

Identifier Type: -

Identifier Source: org_study_id