Ignite Creation Date:
2024-05-05 @ 4:41 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00299858
Status:
COMPLETED
Last Update Posted:
2017-07-07
First Post:
2006-03-03
Brief Title:
Theophylline in Chronic Obstructive Pulmonary Disease
Sponsor:
Ottawa Hospital Research Institute
Organization:
Ottawa Hospital Research Institute
Study Overview
Official Title:
Effect of Theophylline on Exercise Capacity and Lung Function in COPD Patients Receiving Long-acting Inhaled Bronchodilator Therapy
Status:
COMPLETED
Status Verified Date:
2017-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This will be a prospective randomized double-blinded parallel group clinical trial evaluating the short-term effects of theophylline therapy on exercise duration and lung function in patients with chronic obstructive pulmonary disease already receiving both tiotropium and a long-acting beta-agonist salmeterol or formoterol
Detailed Description:
Objective
The primary objectives of this study is to assess the effects of 4 weeks of theophylline therapy on exercise performance and lung function in patients with COPD already receiving combination inhaled long-acting bronchodilator therapy
Background
The latest Canadian COPD guidelines recommend the use of long-acting bronchodilators in patients who continue to experience symptoms despite as-needed use of short-acting bronchodilators Unfortunately patients with severe COPD may continue to experience symptoms despite use of both long-acting beta-agonists and anticholinergics For these patients the Canadian guidelines recommend a trial of theophylline Studies have shown that theophylline can reduce symptoms and improve exercise performance however the use of theophylline is limited by its narrow therapeutic window and multiple drug interactions Despite recommendations it remains unknown whether theophylline provides any additional benefit for COPD patients already receiving combined long-acting bronchodilator therapy No study has evaluated the effect of theophylline in patients already receiving both long-acting beta-agonist and long-acting anticholinergic therapy
Methods
This will be a prospective randomized double-blinded parallel group clinical trial evaluating the short-term effects of theophylline therapy on exercise duration and lung function in patients already receiving both tiotropium and a long-acting beta-agonist salmeterol or formoterol Twenty-four patients with moderate to severe COPD who are already using tiotropium and long-acting beta agonists will be randomized to receive either a 4 weeks of oral theophylline dosed to achieve therapeutic blood levels or b 4 weeks of identical placebo therapy Only patients with stable COPD no exacerbations nor changes in medications over the last 2 months and no contraindications to exercise testing or theophylline use will be enrolled All patients will undergo baseline pulmonary function testing and incremental and constant load exercise testing prior to randomization PFTs and constant load exercise testing will be repeated after 4 weeks of therapy Patients will be instructed to report adverse events and will have their theophylline dose adjusted to ensure therapeutic bloods levels 55-110 umolL prior to repeat testing
Outcome Measurements
The primary outcome of interest will be the effect of theophylline on exercise duration during constant load 75 maximum exercise testing The study will be powered to detect a 20 greater improvement in exercise duration for the theophylline-treated group Secondary outcome measures will include changes in spirometry FEV1 and lung volumes
Anticipated results
Exercise duration on constant load exercise testing was chosen as the primary endpoint of this study because it has been shown to be a reproducible and highly responsive measure for physiologic benefit in COPD It is unknown whether theophylline will provide any additional increase in exercise duration when added to a combined long-acting bronchodilator regimen If an improvement is found with theophylline a follow-up study of larger size and longer duration will be required to investigate whether this benefit will translate into improvements in clinical outcomes such as quality of life or frequency of exacerbations Alternatively if no improvement can be detected the current COPD treatment recommendation should be re-evaluated
The primary objectives of this study is to assess the effects of 4 weeks of theophylline therapy on exercise performance and lung function in patients with COPD already receiving combination inhaled long-acting bronchodilator therapy
Background
The latest Canadian COPD guidelines recommend the use of long-acting bronchodilators in patients who continue to experience symptoms despite as-needed use of short-acting bronchodilators Unfortunately patients with severe COPD may continue to experience symptoms despite use of both long-acting beta-agonists and anticholinergics For these patients the Canadian guidelines recommend a trial of theophylline Studies have shown that theophylline can reduce symptoms and improve exercise performance however the use of theophylline is limited by its narrow therapeutic window and multiple drug interactions Despite recommendations it remains unknown whether theophylline provides any additional benefit for COPD patients already receiving combined long-acting bronchodilator therapy No study has evaluated the effect of theophylline in patients already receiving both long-acting beta-agonist and long-acting anticholinergic therapy
Methods
This will be a prospective randomized double-blinded parallel group clinical trial evaluating the short-term effects of theophylline therapy on exercise duration and lung function in patients already receiving both tiotropium and a long-acting beta-agonist salmeterol or formoterol Twenty-four patients with moderate to severe COPD who are already using tiotropium and long-acting beta agonists will be randomized to receive either a 4 weeks of oral theophylline dosed to achieve therapeutic blood levels or b 4 weeks of identical placebo therapy Only patients with stable COPD no exacerbations nor changes in medications over the last 2 months and no contraindications to exercise testing or theophylline use will be enrolled All patients will undergo baseline pulmonary function testing and incremental and constant load exercise testing prior to randomization PFTs and constant load exercise testing will be repeated after 4 weeks of therapy Patients will be instructed to report adverse events and will have their theophylline dose adjusted to ensure therapeutic bloods levels 55-110 umolL prior to repeat testing
Outcome Measurements
The primary outcome of interest will be the effect of theophylline on exercise duration during constant load 75 maximum exercise testing The study will be powered to detect a 20 greater improvement in exercise duration for the theophylline-treated group Secondary outcome measures will include changes in spirometry FEV1 and lung volumes
Anticipated results
Exercise duration on constant load exercise testing was chosen as the primary endpoint of this study because it has been shown to be a reproducible and highly responsive measure for physiologic benefit in COPD It is unknown whether theophylline will provide any additional increase in exercise duration when added to a combined long-acting bronchodilator regimen If an improvement is found with theophylline a follow-up study of larger size and longer duration will be required to investigate whether this benefit will translate into improvements in clinical outcomes such as quality of life or frequency of exacerbations Alternatively if no improvement can be detected the current COPD treatment recommendation should be re-evaluated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None