Table 1.
RCTs selected for the analysis
| Clinicaltrials number | Title | Investigationnal product | Phase | Starting year | Number of patients enrolled | Percentage of eligible patients |
|---|---|---|---|---|---|---|
| NCT00430729 | Effect of Roflumilast on Exacerbation Rate in Patients With Chronic Obstructive Pulmonary Disease. A 52 Weeks Double Blind Study With 500mcg Roflumilast Once Daily Versus Placebo. Ratio-Study. | Roflumilast | III | 2003 | 1100 | 8.8% |
| NCT01120691 | A 64-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Active Controlled Study to Evaluate the Effect of QVA149 (110/50 μg o.d.) vs NVA237 (50 μg o.d.) and Open-label Tiotropium (18 μg o.d.) on COPD Exacerbations in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD) | Indacaterol/ Glycopyrronium | III | 2010 | 2224 | 2.3% |
| NCT00909779 | A Large Simple Safety Study of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease | Arformoterol | III | 2009 | 841 | 5.3% |
| NCT00419744 | A Phase IIIB, 12-Month, Double-blind, Double-dummy, Randomised, Parallel-group, Multicentre Exacerbation Study of SYMBICORT® pMDI 160/4.5 μg × 2 Actuations Twice-daily and 80/4.5 μg × 2 Actuations Twice-daily Compared to Formoterol Turbuhaler® 4.5 μg × 2 Inhalations Twice-daily in COPD Subjects | Budesonide/ Formoterol | III | 2007 | 1200 | 35.8% |
| NCT01009463 | HZC102871: A 52-week Efficacy and Safety Study to Compare the Effect of Three Dosage Strengths of Fluticasone Furoate/Vilanterol Inhalation Powder With Vilanterol on the Annual Rate of Exacerbations in Subjects With Chronic Obstructive Pulmonary Disease (COPD) | Fluticasone / Vilanterol | III | 2009 | 1626 | 19.1% |
| NCT01126437 | A Randomized, Active-controlled, Double-blind, Double-dummy, Parallel Group Design, Multi-center Trial to Compare the Efficacy and Safety of 2.5 μg and 5 μg Tiotropium Inhalation Solution Delivered by the Respimat Inhaler With Tiotropium Inhalation Capsules 18 μg Delivered by the HandiHaler (TIOSPIR) | Tiotropium (respimat) | III | 2010 | 17,210 | 46.7% |
| NCT01443845 | Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Dose Combinations of Long-acting ß2-agonist (LABA) and Inhaled Corticosteroid (ICS) | Roflumilast | IV | 2011 | 2300 | 5.7% |
| NCT01329029 | Effect of Roflumilast on Exacerbation Rate in Patients With COPD Treated With Fixed Combinations of LABA and ICS. A 52-week, Randomised Double-blind Trial With Roflumilast 500 μg Versus Placebo. The REACT Trial | Roflumilast | IV | 2011 | 1945 | 5.7% |
| NCT00361959 | A Multicentre, Randomised, Double-Blind, Double Dummy, Parallel Group, 104 Week Study to Compare the Effect of the Salmeterol/Fluticasone Propionate Combination Product (SERETIDE) 50/500mcg With Tiotropium Bromide 18 Mcg on the Rate of Exacerbations in Subjects With Severe Chronic Obstructive Pulmonary Disease (COPD) | Fluticasone/ Salmeterol | IV | 2003 | 1270 | 5.0% |
| NCT00563381 | Effect of Inhalation of Tiotropium Once Daily 18 Mcg Versus Salmeterol Twice Daily 50 Mcg on Time to First Exacerbation in COPD Patients (a Randomised, Double-blind, Double-dummy, Parallel Group, One-year Study). | Tiotropium | IV | 2008 | 7376 | 27.2% |
| NCT00115492 | A Randomized, Double-Blind, Parallel Group, 52-week Study to Compare the Effect of the Fluticasone Propionate/Salmeterol DISKUS Combination Product 250/50mcg BID with Salmeterol DISKUS 50mcg BID on the Annual Rate of Moderate/Severe Exacerbations in Subjects with Chronic Obstructive Pulmonary Disease (COPD) | Fluticasone/ Salmeterol | IV | 2004 | 740 | 7.9% |
| NCT02138916 | Randomised, Double-blind, 56 Week Placebo-controlled, Parallel Group, Multicentre, Phase 3 Study to Evaluate the Efficacy and Safety of 2 Doses of Benralizumab in Patients With Moderate to Very Severe COPD With a History of Exacerbations | Benralizumab | III | 2014 | 1626 | 13.9% |
| NCT02579850 | 52-week, Double Blind, Randomized, 2 Active Parallel Arms Study of Fixed Combination CHF 5993 Administered vs Ultibro® in COPD Patients | Béclomethasone/ Formoterol/ Glycopyrronium | III | 2015 | 1534 | 4.1% |
| NCT02465567 | A Randomized, Double-Blind, Multi-Center, Parallel-Group Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 on COPD Exacerbations Over a 52-Week Treatment Period in Subjects With Moderate to Very Severe COPD (Ethos) | Budesonide/ Formoterol/ Glycopyrronium | III | 2015 | 8000 | 32.2% |
| NCT02105961 | Study MEA117113: Mepolizumab vs. Placebo as Add-on Treatment for Frequently Exacerbating COPD Patients Characterized by Eosinophil Level | Mepolizumab | III | 2014 | 660 | 16.3% |
| NCT02296138 | A Randomised, Double-blind, Active-controlled Parallel Group Study to Evaluate the Effect of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination Compared With Tiotropium on Chronic Obstructive Pulmonary Disease (COPD) Exacerbation in Patients With Severe to Very Severe COPD. [DYNAGITO] | Tiotropium/ Olodaterol | III | 2015 | 7800 | 27.7% |