Skip to main content
PMC home page
Thorax logoLink to Thorax
. 2000 Apr;55(4):289–294. doi: 10.1136/thorax.55.4.289

A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease

J A van Noord 1, T Bantje 1, M Eland 1, L Korducki 1, P Cornelissen 1
PMCID: PMC1745719  PMID: 10722768

Abstract

BACKGROUND—A study was undertaken to evaluate and compare the efficacy and safety of tiotropium and ipratropium during long term treatment in patients with stable chronic obstructive pulmonary disease (COPD).
METHODS—288 patients of mean (SD) age 65 (8) years and forced expiratory volume in one second (FEV1) 41 (12)% predicted participated in a 14 centre, double blind, double dummy, parallel group study and were randomised after a run in period of two weeks to receive either tiotropium 18 µg once daily from a dry powder inhaler (HandiHaler; two thirds of patients) or ipratropium 40 µg four times daily from a metered dose inhaler (one third of patients) for a period of 13 weeks. Outcome measures were lung function, daily records of peak expiratory flow (PEF), and the use of concomitant salbutamol. FEV1 and forced vital capacity (FVC) were measured one hour before and immediately before inhalation (mean value of the two measurements on test day 1 was the baseline value while on all other test days it was known as the trough FEV1 and FVC), and 0.5, 1, 2, 3, 4,5, and 6 hours after inhalation of the study drug on days 1, 8,50, and 92.
RESULTS—During treatment tiotropium achieved a significantly greater improvement than ipratropium (p<0.05) in trough, average, and peak FEV1 levels and in trough and average FVC levels. The trough FEV1 response on days 8, 50, and 92 ranged between 0.15 l (95% CI 0.11 to 0.19) and 0.16 l (95% CI 0.12 to 0.20) for tiotropium and between 0.01 l (95% CI -0.03 to 0.05) and 0.03 l (95% CI 0.01to 0.07) for ipratropium. The trough FVC response on days 8, 50,and 92 ranged between 0.34 l (95% CI 0.28 to 0.40) and 0.39 l (95% CI 0.31 to 0.47) for tiotropium and between 0.08 l (95% CI 0.00 to 0.16) and 0.18 l (95% CI 0.08 to 0.28) for ipratropium. On all test days tiotropium produced a greater improvement in FEV1 than ipratropium starting three hours after inhalation (p<0.05). During treatment weekly mean morning and evening peak expiratory flow (PEF) was consistently better in the tiotropium group than in the ipratropium group, the difference in morning PEF being significant up through week 10 and in evening PEF up through week 7 of treatment (p<0.05). The use of concomitant salbutamol was also lower in the tiotropium group (p<0.05). The only drug related adverse event was dry mouth (tiotropium 14.7%, ipratropium 10.3% of patients).
CONCLUSIONS—Tiotropium in a dose of 18 µg inhaled once daily using the HandiHaler was significantly more effective than 40 µg ipratropium four times daily in improving trough, average, and peak lung function over the 13 week period. The safety profile of tiotropium was similar to ipratropium. These data support the use of tiotropium as first line treatment for the long term maintenance treatment of patients with airflow obstruction due to COPD.



Full Text

The Full Text of this article is available as a PDF (167.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnes P. J., Basbaum C. B., Nadel J. A. Autoradiographic localization of autonomic receptors in airway smooth muscle. Marked differences between large and small airways. Am Rev Respir Dis. 1983 Jun;127(6):758–762. doi: 10.1164/arrd.1983.127.6.758. [DOI] [PubMed] [Google Scholar]
  2. Barnes P. J. Muscarinic receptor subtypes in airways. Life Sci. 1993;52(5-6):521–527. doi: 10.1016/0024-3205(93)90310-y. [DOI] [PubMed] [Google Scholar]
  3. Disse B., Reichl R., Speck G., Traunecker W., Ludwig Rominger K. L., Hammer R. Ba 679 BR, a novel long-acting anticholinergic bronchodilator. Life Sci. 1993;52(5-6):537–544. doi: 10.1016/0024-3205(93)90312-q. [DOI] [PubMed] [Google Scholar]
  4. Gross N. J. Ipratropium bromide. N Engl J Med. 1988 Aug 25;319(8):486–494. doi: 10.1056/NEJM198808253190806. [DOI] [PubMed] [Google Scholar]
  5. Gross N. J., Skorodin M. S. Anticholinergic, antimuscarinic bronchodilators. Am Rev Respir Dis. 1984 May;129(5):856–870. doi: 10.1164/arrd.1984.129.5.856. [DOI] [PubMed] [Google Scholar]
  6. Hay J. G., Stone P., Carter J., Church S., Eyre-Brook A., Pearson M. G., Woodcock A. A., Calverley P. M. Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease. Eur Respir J. 1992 Jun;5(6):659–664. [PubMed] [Google Scholar]
  7. Ingram R. H., Jr, Wellman J. J., McFadden E. R., Jr, Mead J. Relative contributions of large and small airways to flow limitation in normal subjects before and after atropine and isoproterenol. J Clin Invest. 1977 Apr;59(4):696–703. doi: 10.1172/JCI108688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kelly C. A., Gibson G. J. Relation between FEV1 and peak expiratory flow in patients with chronic airflow obstruction. Thorax. 1988 Apr;43(4):335–336. doi: 10.1136/thx.43.4.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Macklem P. T. The physiology of small airways. Am J Respir Crit Care Med. 1998 May;157(5 Pt 2):S181–S183. doi: 10.1164/ajrccm.157.5.rsaa-2. [DOI] [PubMed] [Google Scholar]
  10. Maesen F. P., Smeets J. J., Costongs M. A., Wald F. D., Cornelissen P. J. Ba 679 Br, a new long-acting antimuscarinic bronchodilator: a pilot dose-escalation study in COPD. Eur Respir J. 1993 Jul;6(7):1031–1036. [PubMed] [Google Scholar]
  11. Maesen F. P., Smeets J. J., Sledsens T. J., Wald F. D., Cornelissen P. J. Tiotropium bromide, a new long-acting antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive pulmonary disease (COPD). Dutch Study Group. Eur Respir J. 1995 Sep;8(9):1506–1513. [PubMed] [Google Scholar]
  12. Mitchell D. M., Gildeh P., Dimond A. H., Collins J. V. Value of serial peak expiratory flow measurements in assessing treatment response in chronic airflow limitation. Thorax. 1986 Aug;41(8):606–610. doi: 10.1136/thx.41.8.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. O'Connor B. J., Towse L. J., Barnes P. J. Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma. Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):876–880. doi: 10.1164/ajrccm.154.4.8887578. [DOI] [PubMed] [Google Scholar]
  14. Quanjer P. H., Tammeling G. J., Cotes J. E., Pedersen O. F., Peslin R., Yernault J. C. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5–40. [PubMed] [Google Scholar]
  15. Rennard S. I., Serby C. W., Ghafouri M., Johnson P. A., Friedman M. Extended therapy with ipratropium is associated with improved lung function in patients with COPD. A retrospective analysis of data from seven clinical trials. Chest. 1996 Jul;110(1):62–70. doi: 10.1378/chest.110.1.62. [DOI] [PubMed] [Google Scholar]
  16. Siafakas N. M., Vermeire P., Pride N. B., Paoletti P., Gibson J., Howard P., Yernault J. C., Decramer M., Higenbottam T., Postma D. S. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. Eur Respir J. 1995 Aug;8(8):1398–1420. doi: 10.1183/09031936.95.08081398. [DOI] [PubMed] [Google Scholar]
  17. Takahashi T., Belvisi M. G., Patel H., Ward J. K., Tadjkarimi S., Yacoub M. H., Barnes P. J. Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways. Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 1):1640–1645. doi: 10.1164/ajrccm.150.6.7952627. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES