Theophylline in Chronic Obstructive Pulmonary Disease
Information source: Ottawa Hospital Research Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: COPD
Intervention: Theophylline (Drug)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: Ottawa Hospital Research Institute Official(s) and/or principal investigator(s): Nha Voduc, MD, Principal Investigator, Affiliation: Ottawa Hospital Research Institute
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).
Clinical Details
Official title: Effect of Theophylline on Exercise Capacity and Lung Function in COPD Patients Receiving Long-acting Inhaled Bronchodilator Therapy
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Exercise duration during constant load (75% maximum) exercise testing
Secondary outcome: Changes in spirometry (FEV1) Changes in lung volumes
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 umol/L), 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.
Eligibility
Minimum age: 40 Years.
Maximum age: 90 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
clinical diagnosis of COPD, that is at least "moderate" in severity according to GOLD
guidelines (FEV1 60% predicted and FEV1/FVC ratio 70%).
clinically stable (no exacerbations nor changes in medications over the previous two
months.
taking tiotropium 18ug qd and either salmeterol 50ug bid or formoterol 12 ug bid (the use
of inhaled corticosteroids is not required but is permitted as long as there have been no
dose changes over the last 2 months).
Exclusion Criteria:
Lung disease other than COPD (e. g: asthma, interstitial lung disease)
Non-pulmonary comorbidity that may potentially limit exercise capacity (e. g: cardiac
disease, arthritis) or be exacerbated by theophylline use.
History of adverse response to theophylline or condition that may increase likelihood of
adverse reaction with theophylline (cardiac disease, liver disease, renal impairment,
thyroid disease)
Use of theophylline over last two months.
Use of a medication that may potentially interact with theophylline (e. g. warfarin,
digoxin)
Patients currently enrolled (or scheduled to be enrolled) in a pulmonary rehabilitation
program will not be accepted until after completion of the program (as this may
potentially affect exercise performance).
Use of systemic corticosteroid therapy (this may affect peripheral muscle function)
Locations and Contacts
Ottawa Hospital, General campus, Ottawa, Ontario K1H 8L6, Canada
Additional Information
Starting date: October 2006
Last updated: November 10, 2010
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