Published ahead of print on September 22, 2006, doi:10.1164/rccm.200603-416OC
Am. J. Respir. Crit. Care Med., Volume 175, Number 3, February 2007, 235-242
A more recent version of this article appeared on February 1, 2007
Submitted on March 23, 2006
Accepted on September 21, 2006
Clinical Trial of Low-Dose Theophylline and Montelukast in Patients with Poorly Controlled Asthma
Charles G Irvin1, David A Kaminsky1, Nicholas R Anthonisen2, Mario Castro3, Nicola A Hanania4, Janet T Holbrook5, John J Lima6, and Robert A Wise5*
1 University of Vermont School of Medicine, Burlington, VT, USA,
2 University of Manitoba School of Medicine, Winnipeg, Manitoba, Canada,
3 Washington University School of Medicine, St Louis, MO, USA,
4 Baylor University School of Medicine, Houston, TX, USA,
5 Center for Clinical Trials, Johns Hopkins University School of Public Health, Baltimore, MD, USA,
6 Department of Pediatrics, Nemours Children's Clinic, Jacksonville, FL, USA
* To whom correspondence should be addressed. E-mail: rwise{at}jhmi.edu.
Background: Asthma treatment guidelines recommend addition of controller medications for patients with poorly controlled asthma. We compared the effectiveness of once-daily oral controller therapy with either an antileukotriene receptor antagonist (montelukast) or low-dose theophylline added to existing medications in patients with poorly-controlled asthma. Methods: We conducted a randomized, double-masked, placebo-controlled trial in 489 participants with poorly controlled asthma randomly assigned to placebo, theophylline (300 mg/day) or montelukast (10 mg/day). Participants were followed for 24 weeks to measure the rate of episodes of poor asthma control (EPACs) defined by: decreased peak flow, increased beta agonist use, oral corticosteroid use or unscheduled health care visits. Observations: There was no significant difference in EPAC rates (events/person - year) compared to placebo: low-dose theophylline 4.9 (95% CI 3.6 - 6.7; NS); montelukast 4.0 (95% CI 3.0 - 5.4; NS) and placebo 4.9 (95% CI 3.8 - 6.4). Both montelukast and theophylline caused small improvements in pre-bronchodilator FEV1 of borderline significance. Nausea was more common with theophylline only during the first four weeks of treatment. Neither treatment improved asthma symptoms or quality of life. However in patients not on inhaled corticosteroids (ICS), addition of low-dose theophylline significantly (p<0.002) improved asthma control and symptoms as well as lung function. Conclusions: Neither montelukast nor low-dose theophylline lowered the event-rate of poor asthma control in patients with poorly-controlled asthma despite improved lung function. For patients not using ICS, low-dose theophylline improved asthma symptom control more than montelukast or placebo and provides a safe and low-cost alternative asthma treatment.
Key words: Clinical Trial, Quality of Life, Respiratory Function Tests, Bronchodilator Agents, Anti-Asthmatic Agents, Multicenter Studies
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