Rational timing of combination therapy with tiotropium and formoterol in moderate and severe COPD

Claudio Terzano, Angelo Petroianni, Vittoria Conti, Daniela Ceccarelli, Elda Graziani, Alessandro Sanduzzi, Serena D'Avelli

Research output: Contribution to journalArticle

Abstract

Aim: To determine which timing of therapy with formoterol (FOR) and/or tiotropium (TIO) shows the greater and more continuous functional improvement during 24 h in patients with moderate to severe COPD. Methods: In this randomised, blind, crossover study 80 patients with stable COPD (40 moderate and 40 severe) received 5 different bronchodilator 30-day treatments in a random order. Treatments (Tr) were: Tr1: TIO 18 μg once-daily (8 am); Tr2: TIO 18 μg (8 am) + FOR 12 μg (8 pm); Tr3: FOR 12 μg twice-daily (8 am and 8 pm); Tr4: TIO 18 μg (8 am) + FOR 12 μg twice-daily (8 am and 8 pm); Tr5: FOR 12 μg twice-daily (8 am and 8 pm) + TIO 18 μg (8 pm). Spirometries were performed during 24 h (13 steps) on Day1 and Day30. End-points were: gain of FEV1 (ΔFEV1) from baseline of the Day1 and Day30, AUC (Area Under Curve), Dyspnoea Index, and as-needed use of salbutamol. Results: Sixty-eight patients completed all treatments. The greater and continuous daily functional improvement was showed during Tr4 and Tr5 (Day1 +135.8 mL and +119.1 mL; Day30 +160.2 mL, and +160.5 mL, respectively). Daily means of ΔFEV1 were significantly different between single-drug treatments and combination therapy. Dyspnoea was greater in single-drug treatments. Less use of rescue salbutamol was reported in Tr4 (0.80 puffs/die) and Tr5 (0.71 puffs/die). Conclusions: In patients with moderate to severe COPD, combination therapy with tiotropium administered in the morning (Tr4) was the most effective; in patients with prevailing night-symptoms, treatment with tiotropium in the evening (Tr5) reduced symptoms and use of salbutamol. Tr5 showed less variability of FEV1 during the 24 h (CV = 0.256). These results are relevant for opening new ways in clinical practice.

Original languageEnglish
Pages (from-to)1701-1707
Number of pages7
JournalRespiratory Medicine
Volume102
Issue number12
DOIs
Publication statusPublished - Dec 2008

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Keywords

  • COPD Therapy
  • Formoterol
  • Spirometry
  • Tiotropium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Terzano, C., Petroianni, A., Conti, V., Ceccarelli, D., Graziani, E., Sanduzzi, A., & D'Avelli, S. (2008). Rational timing of combination therapy with tiotropium and formoterol in moderate and severe COPD. Respiratory Medicine, 102(12), 1701-1707. https://doi.org/10.1016/j.rmed.2008.07.012