Safety and efficacy of tiotropium in patients switching from HandiHaler to Respimat in the TIOSPIR trial

BMJ Open. 2015 Dec 29;5(12):e009015. doi: 10.1136/bmjopen-2015-009015.

Abstract

Objectives: This post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (≥ 2 months) use of tiotropium HandiHaler 18 µg (HH18) prior to study entry, to evaluate whether there was a difference in risk for patients who switched from HH18 to tiotropium Respimat 2.5 µg (R2.5) or 5 g (R5).

Setting: TIOSPIR (n=17,135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial.

Participants: Patients from TIOSPIR with chronic obstructive pulmonary disease (COPD) and postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity ≤ 0.70, receiving HH18 before study entry, were analysed (n=2784).

Interventions: Patients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2-3 years.

Primary outcomes: time to death (safety) and time to first COPD exacerbation (efficacy).

Secondary outcomes: number of exacerbations and time to first major adverse cardiovascular event (MACE).

Results: Baseline characteristics were similar in all groups. Respimat had a similar mortality risk versus HH18 (vital status follow-up, HR; 95% CI R2.5: 0.87; 0.64 to 1.17; R5: 0.79; 0.58 to 1.07) with no significant differences in the risk and rates of exacerbations and severe exacerbations across treatment groups. Risk of MACE and fatal MACE was similar for Respimat versus HH18 (HR; 95% CI MACE R2.5: 0.73; 0.47 to 1.15; R5: 0.69; 0.44 to 1.08; fatal MACE R2.5: 0.57; 0.27 to 1.19; R5: 0.67; 0.33 to 1.34). Overall risk of a fatal event (on treatment) was lower for R5 versus HH18 (HR; 95% CI R2.5: 0.78; 0.55 to 1.09; R5: 0.62; 0.43 to 0.89).

Conclusions: This analysis indicates that it is safe to switch patients from tiotropium HandiHaler to tiotropium Respimat, and that the efficacy is maintained over the switch.

Trial registration number: NCT01126437; Post-results.

Keywords: COPD; Efficacy; HandiHaler®; Respimat®; Switching; Tiotropium.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aged
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Disease Progression
  • Double-Blind Method
  • Equipment Design
  • Female
  • Forced Expiratory Volume
  • Humans
  • International Cooperation
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nebulizers and Vaporizers*
  • Proportional Hazards Models
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality*
  • Risk Factors
  • Tiotropium Bromide / administration & dosage*
  • Tiotropium Bromide / adverse effects
  • Treatment Outcome

Substances

  • Bronchodilator Agents
  • Tiotropium Bromide

Associated data

  • ClinicalTrials.gov/NCT01126437