Effectiveness and tolerability of high-dose salmeterol in cystic fibrosis.
The efficacy and tolerability of high-dose salmeterol (100 mcg, BID) and albuterol (2.5 mg, BID) were compared with those of albuterol (2.5 mg, BID) in outpatients with cystic fibrosis in a randomized, double-blind, double-dummy, placebo-controlled, crossover study with both short- (4 weeks of each) and long-term (24 weeks of each) treatment periods. The primary outcome measure was the difference in mean change in forced expired volume in 1 sec (FEV(1)) from baseline to the end of each treatment, and secondary measures included changes in forced vital capacity (FVC), forced expiratory flow between 25-75% of FVC (FEF(25-75)), patient-rated weekly symptom scores, number of extra (rescue) albuterol treatments, and number of antibiotic treatments. Tolerability was evaluated by changes in vital signs and adverse events.Thirty-six out of 44 patients enrolled finished the short-term treatment period, and 19 out of 23 who continued the study also finished the long-term treatment period. There was no significant difference in the mean % change in FEV(1) from baseline to completion of 4 weeks with each drug in the short-term treatment period (0.1% vs. 0.06%, albuterol vs. salmeterol; respectively). In the long-term treatment period, there was a significant decrease from baseline in FEV(1) with albuterol vs. salmeterol, as measured after both 12 and 24 weeks of each treatment (-6.2% vs. 1.8%, P = 0.013 after 12 weeks, and -6.5% vs. 1.7%, P = 0.002, after 24 weeks, respectively). In both treatment periods, salmeterol was well-tolerated. While there were more rescue treatments per patient per week with albuterol than with salmeterol treatment in both the short- and long-term periods (0.67 vs. 0.40 and 1.76 vs. 0.74, respectively), rescue treatments were needed significantly more often for only the long-term period with albuterol compared to salmeterol (P = 0.022). Also, there were more antibiotic interventions with albuterol than with salmeterol treatment in both the short- and long-term periods (25 vs. 10 and 56 vs. 42, respectively); however, antibiotics were needed significantly more often for only the short-term period (P = 0.011). In addition, there was a significantly higher symptom score with albuterol vs. salmeterol treatment during the second half of the long-term period (1.24 vs. 0.89, P = 0.001).In conclusion, long-term high-dose salmeterol was equally safe and was associated with better pulmonary function, fewer interventions, and fewer respiratory symptoms compared to standard therapy with albuterol in a population of outpatients with mild to moderate CF.
Department of Pediatric Pulmonology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Nancy L
NL
Hordvik
Paul H
PH
Sammut
C Gerald
CG
Judy
John L
JL
Colombo
D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011674:Pulse; D012016:Reference Values; D000068299:Salmeterol Xinafoate; D013147:Spirometry; D013997:Time Factors; D014797:Vital Capacity / Q000187:drug effects / Q000502:physiology
D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000420:Albuterol