Once versus twice daily formoterol via Novolizer® for patients with moderate to severe COPD—A double-blind, randomised, controlled trial
Introduction
Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which is not fully reversible, usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Drug treatment aims at controlling symptoms and improving exercise tolerance and health status of the patients. Bronchodilators are essential for symptom control, and drugs such as inhaled beta-agonists, anticholinergics or methylxanthines are recommended by national and international guidelines.
Long-acting beta agonists (LABA) are indicated for patients with moderate or severe COPD (6). The LABA formoterol was proved to be superior to placebo [1], and its efficacy is at least comparable to that of salmeterol, theophylline and ipratropium bromide [1], [2], [3], [4].
In many patients with COPD, symptoms are particularly frequent and disturbing in the morning, whereas nocturnal symptoms are uncommon, so that bronchodilators should preferably be inhaled early during the day. In a recent study, patients with asthma inhaled formoterol once daily via the Novolizer®, a refillable, multiple dose dry powder inhaler. The inhalation in the morning provided a bronchodilatory effect for more than 12 h [5]. Considering the experience in asthmatic patients, we hypothesised that formoterol inhaled once per day in the morning could be sufficient for symptom control in patients with moderate to severe COPD.
Since COPD is a disease with a complex therapeutic regimen, suboptimal compliance is frequent among patients. In a recent study, 63% of ambulatory patients were identified as non-adherent [6], and an earlier paper had reported that 60% of patients with moderate to severe COPD were poorly adherent with inhaled corticosteroids [7]. Notably, better adherence of COPD patients was associated with a lower number of hospital visits in the latter investigation. Non-adherence is generally more likely if treatment regimens are lengthier and more complicated [8]. Simpler, once-daily therapies are thought to improve compliance [9], as well as medication regimens that fit well into the patient's daily routine [10]. The once-daily inhalation used in the present study was expected to facilitate better treatment adherence.
The current trial in patients with moderate to severe COPD intended to evaluate if a daily dose of 24 μg formoterol via Novolizer® was of equal efficacy whether inhaled as a single dose in the morning or administered in two divided doses in the morning and in the evening. The primary end-point was the change in pre-dose FEV1 from baseline to the value after 12 weeks of treatment.
Section snippets
Study design
We designed a randomised, double blind, active-controlled, parallel-group, multi-centre study with a 2-week run-in period and a 12-week treatment phase. The study was performed in 47 outpatient centres in Germany. Five study visits (at weeks −2, 0, 4, 8, and 12) were planned, each of which was scheduled in the morning, preferably between 8:00 and 10:00 a.m., prior to the morning dose of study medication.
Eligibility criteria
Male or female patients aged 40–70 years with moderate to severe COPD (Stage II or III
Results
A total of 364 patients were screened for the study, and 321 participants were randomised to treatment between January and November 2004 (Table 1). The most frequent reasons for not being randomised were inclusion/exclusion criteria not met in 20 cases (46.5%), withdrawal of consent (14%), and other reasons (14.0%). About 302 patients completed the study. The most frequent reason for withdrawal was loss to follow-up. The ITT group consisted of 155 randomized patients in Group 1 (24 μg formoterol
Discussion
Most COPD patients experience more symptoms in the morning than in the evening. For example, dyspnoea on exertion is a major complaint which is important mainly during the daytime waking hours. When designing the present trial we hypothesised that inhaling a single dose of 24 μg formoterol in the morning would provide sufficient bronchodilatation and symptom control and would not be inferior to two daily inhalations of 12 μg formoterol. To our knowledge, a study into this question has never been
Acknowledgements
The authors are indebted to the study of physicians of the FoNoCo1 trial for recruiting patients into the study: Prof. Dr. T. Welte, Hannover; Dr. A. Piecyk, Magdeburg; Dr. R. Bamberg, Potsdam; Dr. D. Bauer, St. Ingbert; Dr. E. Baumann, München; Dr. E. Beck, Rüdersdorf; Dr. H.-C. Blum, Dortmund; Dr. U. Botzen, Solingen; Dr. J. Eberhardt, Mettmann; Dr. J. Eller, Berlin; Dr. W. Feußner, Kassel; Dr. H. Fickinger-Woerner, Saarbrücken; Dr. H.W. Fischer, Verden; Dr. H.G. Flack, Hagen; Dr. K.-H.
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Long-acting bronchodilators improve Health Related Quality of Life in patients with COPD
2013, Respiratory MedicineCitation Excerpt :HRQoL/HS were evaluated in all studies using the SGRQ. The study duration ranged from 12 weeks to 12 months, and comparators of formoterol were terbutalin [22], salmeterol [23], ipratropium [24,25], theophylline [26], different formulations of formoterol [27] and placebo [23–29]. Formoterol was tested as dry powder inhaler (DPI) Aerolizer at dose of 12/24 μg bis in die (BID) [2426,27,28], Novolizer 12/24 μg BID [29], Turbohaler 18 μg BID [25], 9 μg BID or BID + 4.5 μg prn [22], and nebulized arformoterol via PARI LC PLUS nebulizer at doses of 15/20/25 μg BID [23,27,28] and 50 μg [23].
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2012, ChestCitation Excerpt :Surprisingly, the effect of long-acting muscarinic antagonists on nighttime symptoms has not been extensively studied, and a validated instrument to assess nighttime COPD symptoms is not currently available. In this study, we used COPD symptom score definitions of Welte et al11 to investigate the effect of treatment on nighttime symptoms as reported daily in patient diaries. Results from these diaries revealed significant improvements from baseline in nighttime symptoms with bid aclidinium vs placebo, which were not observed with daily tiotropium.
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2016, BMJ Open Respiratory ResearchMeyler’s Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions, Sixteenth Edition
2015, Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions