The CLIMB Study

The CLIMB study design

The CLIMB study by Welte and colleagues [1] was a 12-week, randomised double-blind, parallel-group study comparing the efficacy and tolerability of Symbicort® added to tiotropium with tiotropium alone in COPD.

Patients (N = 660, mean age 62 years, forced expiratory volume in 1 second [FEV1] 1.1l, 38% predicted normal) with COPD eligible for inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combination therapy were randomised to receive tiotropium (18 μg) once daily plus either Symbicort (320/9 μg) twice daily or placebo. All patients used terbutaline for symptom relief. The primary efficacy variable was change in FEV1.

The CLIMB study results

Symbicort added to tiotropium provided rapid and sustained improvements in lung function, morning symptoms and activities, health status and a 62% reduction reduced severe exacerbations compared with tiotropium alone in patients with COPD eligible for ICS/LABA combination therapy.

Symbicort added to tiotropium resulted in:

• a significant 6% increase in pre-dose FEV1 and 11% in post-dose FEV1,  measured at the clinic (both P < 0.001), with a more rapid onset of effect versus tiotropium alone. Improvements in pre- and post-dose forced vital capacity and inspiratory capacity were also observed.
• greater improvements in lung function measurements taken at home (morning FEV1 and peak expiratory flow) compared with tiotropium alone.
• significant improvements in COPD symptom scores (breathlessness, night-time awakening, chest tightness and cough) versus tiotropium (all P < 0.001), as assessed by the Global Chest Symptoms Questionnaire (GCSQ) [2].
• significant improvements in morning activities versus tiotropium. Using the validated Capacity of Daily Living in the Morning questionnaire (CDLM) [2],  total activity score significantly improved after just 1 week of treatment with Symbicort added to tiotropium (P = 0.027) and these improvements were sustained and continued to improve over the study period; after 12 weeks, improvements in each of the individual activity scores were significant (getting washed, dried, dressed, eating breakfast, walking around the home early and later) compared with tiotropium alone.
• improvements in health-related quality of life. Approximately 50% of patients in the Symbicort added to tiotropium arm improved their total St George’s respiratory questionnaire score by more than four points compared with 40% in the tiotropium alone group (P = 0.016); this four-point difference has been shown to be clinically significant [3].
• a significant 62% reduction in the number of severe exacerbations (P < 0.001), a 65% reduction in the number of hospitalisations (P = 0.011) and a prolonged time to first severe exacerbation (P < 0.001) and hospitalisations (P = 0.026) compared with tiotropium alone.
• Both treatments were well tolerated.

References

1. Welte T, Miravitlles M, Hernandez P, et al. Efficacy and tolerability of budesonide/formoterol added to Spiriva in patients with chronic obstructive disease. Am J Respir Crit Care Med 2009; 180:1–10.
2. Partridge MR, Miravitlles M, Ståhl E, et al. Development and validation of the Capacity of Daily Living during the Morning questionnaire and Global Chest Symptoms Questionnaire for patients with COPD. Eur Respir J 2009; Published online 6 November 2009; doi:10.1183/09031936.00123709.
3. Jones P, Spencer S, Adie S. The St George's Respiratory Questionnaire Manual, Version 2.1. 2003. St George's Hospital Medical School. London, UK.