Efficacy and safety of oxitropium bromide, theophylline and their combination in COPD patients: a double-blind, randomized, multicentre study (BREATH Trial)

Abstract

We compare the efficacy including spirometry, peak expiratory flow (PEFR) and quality of life and safety of an 8-week treatment with inhaled oxitropium, theophylline or their combination in patients with mild-to-severe chronic obstructive pulmonary disease (COPD). We conducted a multicentre, double-blind, double-dummy randomized, parallel-group study at 29 Italian outpatients clinics. A group of 236 patients with mild-to-severe COPD (baseline FEV1 < or = 70% of predicted value) were recruited. Treatments were as follows: Inhaled oxitropium bromide 200 microg (N=75), sustained-release oral theophylline 300 mg (N=81) or their combination (N=80), taken twice daily. Spirometry (FEV1 and FVC) was evaluated every 4 weeks, and morning and evening PEFR (before and 2-4 h after drug intake) was measured daily. Symptoms, cough and dysponea, were recorded daily. Health status was evaluated at baseline and week 8 using the disease specific St George' Respiratory Questionnaire (SGRQ). Any adverse event occurring during the treatment period was recorded on a diary card. FEV1 and FVC improved in all the groups at 4 and 8 weeks, but the difference between treatment groups did not reach statistically significant levels. Differences between groups in pre-dosing morning and evening PEFR were not significant. Post-dosing morning and evening PEFR were increased and the largest increase was seen in patients treated with both drugs. However, differences between groups was significant only for evening values (P=0.008). The proportion of patients who experienced a decrease in symptoms was high in all groups but no differences among groups were observed. SGRQ total scores decreased in all treatment groups after 8 weeks, particularly in the oxitropium and combination groups. Clinically significant change (> or = 4 units) was only observed in patients treated with oxitropium bromide whether with or without theophylline. Adverse events related to treatments were higher in the group treated with theophylline alone (P < 0.02). We conclude that inhaled oxitropium bromide alone was associated with an improvement in FEV1, PEFR and symptoms in patients with COPD that was not statistically different from that of oral theophylline alone or of the combination of both drugs. Oxitropium bromide in combination with theophylline provided a greater improvement in evening post-dosing PEFR. Oxitropium bromide alone or in combination with theophylline improved the quality of life better than theophylline alone.

Use of Tiotropium Bromide for Pre-operative Treatment in Chronic Obstructive Pulmonary Disease Patients: Comparison with Oxitropium Bromide

“…The replacement of oxitropium bromide with tiotropium bromide significantly increases pulmonary function in patients with COPD and the improvement also involves small airways (31). COPD may increase the incidence of refractory supraventricular arrhythmias following surgery (35), and β2-agonist usage in COPD patients increases the risk of adverse cardiovascular events (36) (39). In our study, anticholinergic drugs were administered in combination with other therapies in both groups.…”

Effect of add-on therapy of tiotropium in COPD treated with theophylline

“…In addition, a combination of the short-acting anti-cholinergic oxitropium and theophylline improved QOL to a signifi cantly greater extent than did each monotherapy (Bellia et al 2002). Furthermore, combination treatment with a short-acting β 2 -agonist, a short-acting anticholinergic agent, and oral theophylline led to signifi cantly greater improvement in FEV 1 compared with the results of monotherapy, without any severe adverse effects (Karpel et al 1994).…”

Pharmacological treatment of chronic obstructive pulmonary disease

“…However, the interindividual variability of the bronchodilating effect can be high. The efficacy of combining either short or long-acting β 2 -agonists with anticholinergics (COMBIVENT 1994; van Noord et al 2000, 2006), anticholinergics and theophylline (Bleecker and Britt 1991; Bellia et al 2002), and all three classes of bronchodilators is known (Nishimura et al 1995). A fixed inhaled combination of albuterol and ipratropium is available.…”