Background
Methods
Patients
Analysis of eligibility of patients with COPD to RCTs
Results
RCTs
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% |
Description of eligibility criteria (Table 2)
Criterion | Total number of trials setting the criterion | Cut-off values of the criterion | Number of trials setting the criterion | Availability of data in Initiative BPCO database | Percentage of patients excluded by the criterion | |
---|---|---|---|---|---|---|
Demographics | Minimum age | 16 (100%) | 40 years | 16 (100%) | yes | 1.1% |
Maximum age | 3 (18.8%) | 80 years | 2 (12.5%) | yes | 5.3% | |
85 years | 1 (6.3%) | yes | 0.8% | |||
Disease diagnosis and severity | Smoking history | 15 (93.8%) | Current or former smoker | 15 (93.8%) | yes | 4.9% |
At least 10 PY | 11 (68.8%) | yes | 17.6% | |||
At least 15 PY | 1 (6.3%) | yes | 20.2% | |||
At least 20 PY | 2 (12.5%) | yes | 25.1% | |||
Airway obstruction | 16 (100%) | FEV1/FVC < 0,7 | 16 (100%) | yes | 0% | |
Maximum FEV1a | 15 (93.8%) | 49% (GOLD 3 threshold) | 8 (50%) | yes | 54.4% | |
79% (GOLD 2 threshold) | 1 (6.3%) | yes | 9.5% | |||
70% | 3 (18.8%) | yes | 22.7% | |||
65% | 2 (12.5%) | yes | 31.2% | |||
60% | 1 (6.3%) | yes | 45% | |||
Minimum FEV1 | 1 (5.5%) | 21% | 2 (12.5%) | yes | 8.8% | |
Minimum exacerbation rate during the previous year | 14 (87.5%) | 1 event | 10 (62.5%) | yes | 36.4% | |
2 events | 4 (25%) | yes | 62.2% | |||
Maximum exacerbation rate during the previous yearb | 13 (81.3%) | 24 events | 2 (12.5%) | yes | 0% | |
12 events | 8 (50%) | yes | 0.1% | |||
9 events | 3 (18.8%) | yes | 0.8% | |||
Disease control | COPD symptoms | 4 (25%) | Evidence of chronic productive cough | 2 (12.5%) | no | Uncollected data (assumed 0%) |
mMRC score > 1 | 1 (6.3%) | |||||
CAT > 10 | 1 (6.3%) | |||||
Concomitant treatments restrictionsc | Long term oxygen therapy | 7 (43.8%) | < 12 h/day | 1 (6.3%) | use of oxygenotherapy assessed | 11.8% |
< 15 h/day | 1 (6.3%) | |||||
< 16 h/day | 1 (6.3%) | |||||
Not daily | 4 (25%) | |||||
Oral corticosteroids | 6 (37.5%) | Forbidden | 4 (25%) | Intake of OCS assessed | 3.0% | |
< 10 mg/day | 2 (12.5%) | |||||
Previous participation in a pulmonary rehabilitation program | 3 (18.8%) | Forbidden | 3 (18.8%) | no | Uncollected data (assumed 0%) | |
Comorbidities restrictionsd | Concomitant pulmonary diseases | 15 (93.8%) | Forbidden | 15 (93.8%) | Only asthma assessed | 13.1% |
History of pulmonary surgery | 7 (43.8%) | Lobectomy | 4 (25%) | Only transplantation assessed | 0% | |
Lung volume reduction | 6 (37.5%) | |||||
Transplantation | 2 (12.5%) | |||||
History of cancer | 8 (50%) | Forbidden | 1 (6.3%) | no | Uncollected data (assumed 0%) | |
Forbidden if within 1 year | 1 (6.3%) | |||||
Forbidden if within 5 years | 6 (37.5%) | |||||
Cardiovascular comorbidities (including arterial hypertension, heart failure, myocardial infarction and arrythmias) | 10 (62.5%) | Forbidden | 10 (62.5%) | Cardiovascular comorbidities assessed | 16.1% | |
Endocrine disorders | 5 (31.3%) | No diabetes | 2 (12.5%) | yes | 13.6% | |
No thyrotoxicosis | 3 (18.8%) | No | Uncollected data(assumed 0%) | |||
No obesity (BMI > 45 kg/m2) | 1 (6.3%) | No | Uncollected data(assumed 0%) | |||
Renal impairement | 4 (22.2%) | No moderate or severe renal failure | 3 (18.8%) | No | Uncollected data(assumed 0%) | |
Allergic status | 3 (18.8%) | No atopic status | 2 (12.5%) | yes | 11% | |
No allergic rhinitis | 3 (18.8%) | yes | 21.2% | |||
History or current drug or alcohol abuse | 8 (50%) | Forbidden | 8 (504%) | No | Uncollected data(assumed 0%) | |
Compliance | History of poor compliance to medication prescription | 3 (18.8%) | Forbidden | 3 (18.8%) | No | Uncollected data(assumed 0%) |
Pregnancy and breastfeeding | Pregnancy and breastfeeding | 8 (50%) | Forbidden | 8 (50%) | No | Uncollected data (assumed 0%) |