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Completed

NCT Number: NCT01112241

Bronchodilator Responsiveness in Obliterative Bronchiolitis

This study has been designed to provide a substantial evidence of acute bronchodilator responsiveness to two sequentially inhaled drugs, a beta2-agonist (i.e., albuterol) and an anticholinergic (i.e., tiotropium bromide), in a group of patients who developed obliterative bronchiolitis after hematopoietic stem cell transplantation.

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Key information

Conditions

Obliterative Bronchiolitis Bronchial Diseases Bronchiolitis Bronchiolitis Obliterans Bronchitis Lung Diseases Lung Diseases, Obstructive Respiratory Tract Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Unit of Preventive and Occupational Medicine - Laboratory of Respiratory Pathophysiology, University Hospital San Martino

Genoa, 16132, Italy

About this study

Obliterative bronchiolitis is a life-threatening non-infectious pulmonary complication of allogeneic hematopoietic stem cell transplantation (HSCT). It is characterized by the development of an obstructive abnormality which has been considered to be insensitive to bronchodilator treatments. However, this knowledge stems from measurements of forced expiratory volume in 1 s (FEV1) which is relatively insensitive to changes in small airway caliber. Moreover, it is known from studies in chronic obstructive pulmonary disease that symptoms improve after bronchodilator treatment even when FEV1 is minimally increased and correlate with the reduction of lung hyperinflation, which is the major consequence of severe expiratory airflow limitation. Therefore, measurements of airway caliber by parameters not affected by volume history and absolute lung volumes are preferable for assessing the effect of bronchodilator interventions.

In the current study, the bronchodilators responsiveness will be assessed by using not only spirometry but also measurements of absolute lung volumes and the forced expiratory flow of a partial maneuver (V'part) started from submaximal lung inflation, thus free of volume history effects.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Obliterative bronchiolitis (OB) following allogeneic HSCT
  • FEV1 to slow inspiratory vital capacity (VC) ratio (FEV1/VC)<5th percentile
  • FEV1 <75% predicted or absolute FEV1 fall >10% of pre-HSCT value
  • evidence of OB by computed tomography scanning
  • negative microbiological yields in bronchoalveolar lavage fluid
  • chronic graft-versus-host disease score >0
  • negative history for bronchial asthma, chronic obstructive pulmonary disease or other significant respiratory disease.

Exclusion criteria

  • inability to perform lung function maneuvers
  • pre-existent chronic lung disease other than OB

Treatment and study plan

albuterol plus tiotropium

Drug

Four separate doses of 100 μg of albuterol and 18 μg of tiotropium bromide. Albuterol will be given by a metered-dose inhaler connected to a valved-holding chamber and tiotropium by a dry-powder device.

Other names: Ventolin® and Spiriva®

Primary outcomes

  1. Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, FEV1 increments ≥12 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FEV1, expressed in liters (L), after bronchodilators - FEV1 (L) before bronchodilators/FEV1 (L) before bronchodilators x 100].

  2. Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, FEV1 increments ≥0.20 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FEV1 (L) after bronchodilators - FEV1 (L) before bronchodilators].

  3. Per Cent Change of Forced Vital Capacity (FVC) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, FVC increments ≥12 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FVC, expressed in liters (L), after bronchodilators - FVC (L) before bronchodilators/FVC (L) before bronchodilators x 100].

  4. Absolute Change of Forced Vital Capacity (FVC) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, FVC increments ≥0.20 liters (L) compared with baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to the American Thoracic Society-European Respiratory Society standard criteria [Pellegrino et al. Eur Respir J 2005; 26: 948-968]. They were calculated as follows: [FVC (L) after bronchodilators - FVC (L) before bronchodilators].

  5. Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, V'max increments ≥40 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to Pellegrino et al. [Chest 1998; 114:1607-1612]. They were calculated as follows: [V'max, expressed in liters.second-1 (L.s-1), after bronchodilators - V'max (L.s-1) before bronchodilators/V'max (L.s-1) before bronchodilators x 100].

  6. Per Cent Change of Partial Forced Expiratory Flow (V'Part) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, V'part increments ≥40 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to Pellegrino et al. [Chest 1998; 114:1607-1612]. They were calculated as follows: [V'part, expressed in liters.second-1 (L.s-1), after bronchodilators - V'part (L.s-1) before bronchodilators/V'part (L.s-1) before bronchodilators x 100].

  7. Per Cent Change of Residual Volume (RV) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, RV decrements ≥10 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [RV, expressed in liters (L), before bronchodilators - RV (L) after bronchodilators/RV (L) after bronchodilators x 100].

  8. Absolute Change of Residual Volume (RV) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, RV decrements ≥0.30 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [RV (L), before bronchodilators - RV (L) after bronchodilators].

  9. Per Cent Change of Functional Residual Capacity (FRC) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, FRC decrements ≥10 per cent as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [FRC, expressed in liters (L), before bronchodilators - FRC (L) after bronchodilators/FRC (L) after bronchodilators x 100].

  10. Absolute Change of Functional Residual Capacity (FRC) After Bronchodilators

    Time frame: Baseline and 90 min after bronchodilators

    Following albuterol plus tiotropium inhalation, FRC decrements ≥0.30 liters (L) as compared to baseline, in an individual subject, were considered as evidence of response to bronchodilators, according to O'Donnell et al. [Eur Respir J 2001; 18: 914-920]. They were calculated as follows: [FRC (L), before bronchodilators - FRC (L) after bronchodilators].

Sponsors and collaborators

Lead sponsor

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Other

Registry information

Official study title

Acute Bronchodilator Responsiveness in Obliterative Bronchiolitis (OB) Following Hematopoietic Stem Cell Transplantation

Acronym: BD-OB

Important dates

Study start
2010
Primary completion
2010
Study completion
2010
First posted
Apr 28, 2010
Registry last updated
Mar 2, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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