Bronchodilator Responsiveness in Obliterative Bronchiolitis

NCT01112241 | Completed Phase 4 Results

• 1 other identifier: BOS-01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obliterative Bronchiolitis

Keywords

Obliterative bronchiolitis; Bronchodilator responsiveness; Partial forced expiratory flow; Lung volumes

Outcome Measures

Primary Outcomes (10)

• Per Cent Change of Forced Expiratory Volume in 1 Second (FEV1) 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: \[FEV1, expressed in liters (L), after bronchodilators - FEV1 (L) before bronchodilators/FEV1 (L) before bronchodilators x 100\].

  Baseline and 90 min after bronchodilators

• Absolute Change of Forced Expiratory Volume in 1 Second (FEV1) 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: \[FEV1 (L) after bronchodilators - FEV1 (L) before bronchodilators\].

  Baseline and 90 min after bronchodilators

• Per Cent Change of Forced Vital Capacity (FVC) 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: \[FVC, expressed in liters (L), after bronchodilators - FVC (L) before bronchodilators/FVC (L) before bronchodilators x 100\].

  Baseline and 90 min after bronchodilators

• Absolute Change of Forced Vital Capacity (FVC) 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: \[FVC (L) after bronchodilators - FVC (L) before bronchodilators\].

  Baseline and 90 min after bronchodilators

• Per Cent Change of Instantaneous Maximal Forced Expiratory Flow (V'Max) 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: \[V'max, expressed in liters.second-1 (L.s-1), after bronchodilators - V'max (L.s-1) before bronchodilators/V'max (L.s-1) before bronchodilators x 100\].

  Baseline and 90 min after bronchodilators

• Per Cent Change of Partial Forced Expiratory Flow (V'Part) 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: \[V'part, expressed in liters.second-1 (L.s-1), after bronchodilators - V'part (L.s-1) before bronchodilators/V'part (L.s-1) before bronchodilators x 100\].

  Baseline and 90 min after bronchodilators

• Per Cent Change of Residual Volume (RV) 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: \[RV, expressed in liters (L), before bronchodilators - RV (L) after bronchodilators/RV (L) after bronchodilators x 100\].

  Baseline and 90 min after bronchodilators

• Absolute Change of Residual Volume (RV) 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: \[RV (L), before bronchodilators - RV (L) after bronchodilators\].

  Baseline and 90 min after bronchodilators

• Per Cent Change of Functional Residual Capacity (FRC) 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: \[FRC, expressed in liters (L), before bronchodilators - FRC (L) after bronchodilators/FRC (L) after bronchodilators x 100\].

  Baseline and 90 min after bronchodilators

• Absolute Change of Functional Residual Capacity (FRC) 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: \[FRC (L), before bronchodilators - FRC (L) after bronchodilators\].

  Baseline and 90 min after bronchodilators

Study Arms (1)

albuterol-tiotropium

EXPERIMENTAL

At visit 1, lung function measurements will be performed in triplicate before and 90 min after inhaling four separate doses of 100 μg of albuterol (Ventolin®) and soon after 18 μg of tiotropium bromide \[Spiriva®\] to ensure maximal or near-maximal bronchodilation. Albuterol will be given by a metered-dose inhaler connected to a valved-holding chamber (Volumatic®) and tiotropium by a dry-powder device (Handihaler®).

Drug: albuterol plus tiotropium

Interventions

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.

Also known as: Ventolin® and Spiriva®

albuterol-tiotropium

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (1)

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

Genoa, 16132, Italy

Location

Related Publications (3)

• Pellegrino R, Rodarte JR, Brusasco V. Assessing the reversibility of airway obstruction. Chest. 1998 Dec;114(6):1607-12. doi: 10.1378/chest.114.6.1607.

  PMID: 9872196 BACKGROUND

• Barisione G, Bacigalupo A, Crimi E, Van Lint MT, Lamparelli T, Brusasco V. Changes in lung volumes and airway responsiveness following haematopoietic stem cell transplantation. Eur Respir J. 2008 Dec;32(6):1576-82. doi: 10.1183/09031936.0139807. Epub 2008 Aug 6.

  PMID: 18684842 BACKGROUND

• Barisione G, Bacigalupo A, Crimi E, Brusasco V. Acute bronchodilator responsiveness in bronchiolitis obliterans syndrome following hematopoietic stem cell transplantation. Chest. 2011 Mar;139(3):633-639. doi: 10.1378/chest.10-1442. Epub 2010 Aug 19.

  PMID: 20724742 RESULT

MeSH Terms

Conditions

Bronchiolitis Obliterans

Interventions

Albuterol; Tiotropium Bromide

Condition Hierarchy (Ancestors)

Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Dr. Giovanni Barisione, MD
• Organization: Azienda Ospedaliera Universitaria San Martino, Genova, Italy

giovanni.barisione@hsanmartino.it

+39 010 5553367

Study Officials

• Giovanni Barisione, MD

  Unit of Preventive and Occupational Medicine, University Hospital San Martino, Genoa, Italy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 27, 2010
• First Posted: April 28, 2010
• Study Start: April 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: March 2, 2011
• Results First Posted: February 23, 2011

Record last verified: 2010-04

Locations

IT (1)