Ref ID 33
Author / Title / Reference / YrVincken W, van Noord J, Greefhorst A. et al. Improved health outcomes in patients with COPD during 1 yr's treatment with Tiotropium. Eur Respir J 2002: 19: 209-216 Dutch / Belgian Tiotropium Study Group
N=N=535 Duration=1 yr Location=29 sites in Netherlands and Belgium
Research DesignTwo one yr studies incorporating a randomised double blind, double dummy parallel group design.
Pts from the Van Noord et al 2000 trial continued into a 1yr RCT and the current study by Vincken et al 2002 describes the combined results of the Van Noord trial and a second large multi centre 1 yr trial.
AimHealth outcome evaluation over a 1 yr period
Operational DefinitionFEV1 <65% of the predicted normal value and <70% of FVC
PopulationCOPD (Asthma excluded)
InterventionTiotropium 18ug once daily dry powder capsule inhaled via a pharmaceutical company device
ComparisonIpratropium 40ug q.i.d. via a MDI
OutcomesSpirometric results, PEFR, Salbutamol use and effects on dyspnoea, HRQoL, exacerbations

Short and long acting beta agonists and inhaled anticholinergic medications were not permitted.


Concomitant use of theophyllines & inhaled steroids were allowed.


Salbutamol MDI 100ug as needed for acute symptom relief.


Mean age=64yrs


Sex=85% Male


Ethnic origin=Not detailed


Tiotropium was superior to Ipratropium (p<0.05) at all time points on all test days except for the first 2h following the first dose and up to 1h after the dose 1 wk later.


At the end of 1 yr, trough FEV1 was 120 ml above day 1 baseline for pts receiving Tiotropium, and had declined by 30ml for those receiving Ipratropium (difference of 150ml between groups, p<0.001 at all time points).


FVC paralleled the FEV1 results.


Spirometry results were consistent across centres.


Throughout the 1 yr treatment, morning and evening PEFR improved significantly more in the Tiotropium group than in the Ipratropium group (p<0.01 at all wkly intervals).


Tiotropium significantly improved all three components of the TDI, as well as the focal score, on all test days compared to Ipratropium (p<0.05).


Proportion of patients achieving a clinically meaningful difference in TDI score (improvement ≥ 1 unit) at 1 year was significantly greater tiotropium group (31%) than the ipratropium groups (18%, p=0.004)

Use of as needed (rescue) Salbutamol

On average, pts receiving Tiotropium self-administered approx four fewer inhalations of Salbutamol/wk-1 compared to pts receiving Ipratropium (p<0.05 for 40 to 52 wks).

Health Related Quality of Life

Over the 1 yr treatment period, the SGRQ total score decreased (improved) in both groups, but gradually returned towards baseline in the Ipratropium group. Improvements were maintained over the yr in the Tiotropium group, and were superior to Ipratropium (difference of 3.30 ± 1.13, p<0.05).


Proportion of patients achieving a clinically meaningful improvement of 4 units in SGRQ total score at 1 year was significantly greater in tiotropium group (52%) than the ipratropium groups (35%, p=0.001)


Tiotropium reduced the number of exacerbations (by 24%, p<0.01), and increased time to first exacerbation (p<0.01) and time to first hospitalisation for a COPD exacerbation (p<0.05) compared with Ipratropium.


Proportion of patients hospitalised for COPD exacerbation was 7.3 % (tiotropium) and 11.7% (ipratropium), p=0.11


Number of hospitalisation/patient/year was 38% lower in tiotropium group (0.10 versus 0.16, p=0.08)

Adverse Events

Apart from an increased incidence of dry mouth in the Tiotropium group, adverse events were similar between treatments.

SIGN Quality Rating++
Hierarchy of Evidence1b
Grading Comments

13% of pts in each treatment group were discontinued due to drug expiration. Although re supply of drugs was planned, it was unnecessary, as the target sample size had been attained due to the lower than expected frequency of withdrawals. Pts who could not complete all visits due to drug expiration were requested to discontinue the study drug at the 9/12 visit but were considered complete pts. The ITT principle was used.

From: Appendix F, Evidence tables

Cover of Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease: Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and Secondary Care [Internet].
NICE Clinical Guidelines, No. 101.
National Clinical Guideline Centre (UK).
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