Efficacy of Fixed Combination of Beclometasone + Formoterol + Glycopyrrolate Versus Foster® in COPD (TRILOGY)
A Phase 3 Randomised Double Blind Randomised Parallel Multinational Trial Comparing a Fixed Combination of Beclometasone + Formoterol + Glycopyrrolate to Foster® in Patients With Chronic Obstructive Pulmonary Disease
調査の概要
詳細な説明
This 52-week randomised 2 parallel groups study evaluated the superiority of fixed triple therapy with Inhaled Corticosteroid (ICS) / Long-Acting β2-Agonist (LABA) / Long-Acting Muscarinic Antagonist (LAMA) compared with ICS/LABA in patients with severe to very severe diagnosed of COPD.
Patients' eligibility was checked during the screening visit including the review of medical history, spirometry assessments, routine labs, physical examination, 12-lead electrocardiogram (ECG), vital signs measurement, prior to entering a 2-week open-label run-in period with BDP/FF to establish a baseline.
After the run-in period, eligible patients were randomised, to either fixed triple therapy BDP/FF/GB or BDP/FF treatment group. During the 52-week treatment period, patients who completed the study did have 5 subsequent visits post randomisation scheduled respectively after 4, 12, 26, 40, and 52 weeks of treatment. During these visits, pre-dose and post-dose spirometry, 12-lead ECG, vital signs, and dyspnoea assessments were performed. Rescue medication use, compliance with the treatment, and EXACT-PRO questionnaire [EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT): a patient-reported outcome (PRO)] were recorded daily (via an electronic diary) during the run-in and randomised treatment periods.
For pharmacovigilance purposes, adverse events (AE) were recorded from the time of patient informed consent signature until subject's study participation ended (Week 52 or early discontinuation).
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Szeged、ハンガリー、6722
- Dr Beatrix BALINT
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Male or female adults aged ≥ 40 years with a diagnosis of COPD
- Current smokers or ex-smokers
- A post-bronchodilator Forced Expiratory Volume in the 1st Second (FEV1) < 50% of the predicted normal value and a post- bronchodilator FEV1/ Forced Vital Capacity (FVC) < 0.7
- At least one exacerbation in the 12 months preceding the screening visit
Exclusion Criteria:
- Pregnant or lactating women
- Diagnosis of asthma or history of allergic rhinitis or atopy
- Patients treated with non-cardioselective β-blockers in the month preceding the screening visit
- Patients treated for exacerbations in the 4 weeks prior to screening visit
- Patients treated with long-acting antihistamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study or if taken as PRN
- Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
- Known respiratory disorders other than COPD
- Patients who have clinically significant cardiovascular condition
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Beclometasone/Formoterol/Glycopyrrolate
CHF 5993 pMDI 100/6/12.5
µg 2 inhalations bid
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Active drug tested
他の名前：
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アクティブコンパレータ：Beclometasone/Formoterol
Foster® 100/6 µg 2 inhalations bid
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Active comparator
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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1_Change From Baseline in Pre-dose Morning Forced Expiratory Volume in the 1st Second (FEV1) -- at Week 26
時間枠：Baseline (Week 0), Week 26.
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Changes from baseline in pre-dose morning FEV1 to visit at Week 26. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. |
Baseline (Week 0), Week 26.
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2_Change From Baseline in 2-hour Post-dose FEV1 -- at Week 26
時間枠：Baseline (Week 0) to 2-hour post-dose at Week 26.
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Change from baseline in 2-hour post-dose FEV1, at Week 26. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. |
Baseline (Week 0) to 2-hour post-dose at Week 26.
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3_Transition Dyspnoea Index (TDI) Focal Score -- at Week 26
時間枠：Baseline (Week 0), Week 26.
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Transition Dyspnoea Index (TDI) focal score is a symptom-based variable tool, used to assess breathlessness and the impact of intervention. BDI/TDI is a clinical rating method based on a validated tool that measures the impact of dyspnoea based on 3 domains: functional impairment, magnitude of task, and magnitude of effort. BDI focal score is the baseline value from which TDI focal score is assessed. BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (i.e. from 0 to 12). Change from baseline in dyspnoea severity was measured using the TDI. TDI score ranges from -3 (major deterioration) to +3 (major improvement) for each domain, with the TDI focal score consisting of the sum of each domain (i.e. from -9 to +9). A higher total score indicates improvement, while a lower or negative score indicates worsening symptoms. BDI=Baseline Dyspnoea Index TDI=Transition Dyspnoea Index |
Baseline (Week 0), Week 26.
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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4_Change From Baseline in Pre-dose Morning FEV1 -- at All the Other Clinic Visits
時間枠：Baseline (Week 0), Week 4. 12, 40, 52.
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Change from baseline in pre-dose morning FEV1, at all the other clinic visits. Please note: results at visit Week 26, are presented as the primary outcome measure #1 for this study. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. |
Baseline (Week 0), Week 4. 12, 40, 52.
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5_Change From Baseline to the Average in Pre-dose Morning FEV1 -- Over the Treatment Period
時間枠：Baseline (Week 0), Week 4, 12, 26, 40, 52.
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Changes from baseline for the average in pre-dose morning FEV1 over the treatment period. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. |
Baseline (Week 0), Week 4, 12, 26, 40, 52.
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6_Number of Participants Defined as Responders Wrt. to FEV1 -- Change From Baseline in Pre-dose Morning FEV1 ≥100 mL -- at Week 26 and Week 52
時間枠：Baseline (Week 0), Week 26, Week 52.
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Number of participants defined as responders wrt. to FEV1 -- at Week 26 and Week 52. FEV1 response was defined as a change from baseline in pre-dose morning FEV1 of ≥100 mL. If the change from baseline was <100 mL, the patient was classified as a non-responder in terms of FEV1. Subjects with missing pre-dose morning FEV1 value at the pre-specified tested time points were also classified as non-responders. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. |
Baseline (Week 0), Week 26, Week 52.
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7_Change From Baseline in 2-hour Post-dose of FEV1 -- at All the Other Clinic Visits
時間枠：Baseline (Week 0), Week 4, 12, 40, 52.
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Change from baseline in 2-hour post-dose of FEV1, at all the other clinic visits. Please note: a) results at visit Week 26, are presented as the primary outcome measure #2 for this study; b) for Week 0, the measurement shown in the results table below was made 2 h after the baseline measurement i.e. pre-treatment at study baseline. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. |
Baseline (Week 0), Week 4, 12, 40, 52.
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8_Change From Pre-dose to 2-hour Post-dose FEV1 -- at All Study Visits
時間枠：Week 4, 12, 26, 40, 52.
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Change from pre-dose to 2-hour post-dose value of FEV1, at study visits on Week 4, 12, 26, 40, and 52. FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath. |
Week 4, 12, 26, 40, 52.
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9_Transition Dyspnoea Index (TDI) Focal Score -- at All Study Visits
時間枠：Baseline (Week 0), Week 4, 12, 40, 52.
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TDI focal score is a symptom-based tool, used to assess breathlessness and the impact of intervention. BDI/TDI is a clinical rating method based on a validated tool that measures the impact of dyspnoea on 3 domains: functional impairment, magnitude of task, and magnitude of effort. TDI tool and its scoring system are defined in the outcome measure #3 of this PRS study entry. Please note: Results at Week 26, are presented as the primary outcome measure #3 for this PRS study entry. BDI=Baseline Dyspnoea Index TDI=Transition Dyspnoea Index |
Baseline (Week 0), Week 4, 12, 40, 52.
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10_Number of Participants With Transition Dyspnoea Index (TDI) Response (Focal Score ≥1) -- at Week 26 and Week 52
時間枠：Week 26, Week 52.
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Number of participants with transition dyspnoea index (TDI) response (focal score ≥1) -- at Week 26 and Week 52. TDI tool and its scoring system are defined in the outcome measure #3 of this PRS study entry. TDI response was defined as a TDI focal score of ≥1. If the TDI focal score was <1, the patient was classified as a non-responder in terms of TDI. Patients with missing TDI focal score at the pre-specified tested time points were also classified as non-responders. |
Week 26, Week 52.
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11a_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Total Score
時間枠：Baseline (Week 0), Week 4, 12, 26, 40, 52.
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Change from baseline in Saint George's respiratory questionnaire (SGRQ) Total score. SGRQ is a 76-item questionnaire developed to measure health in chronic airflow limitation. SGRQ consists of scores from three component that are used to calculate the total score: Symptoms, Activity, and Impacts on daily life. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, and Week 4, 12, 26, 40, 52). The Total score range is from 0 to 100 (0=Best, 100=Worst); lower scores correspond to better health. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). |
Baseline (Week 0), Week 4, 12, 26, 40, 52.
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11b_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Symptoms Score
時間枠：Baseline (Week 0), Week 4, 12, 26, 40, 52.
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Change from baseline in Saint George's respiratory questionnaire (SGRQ) -- Symptoms Score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Symptoms. The Symptoms score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. |
Baseline (Week 0), Week 4, 12, 26, 40, 52.
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11c_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Impacts Score
時間枠：Baseline (Week 0), Week 4, 12, 26, 40, 52.
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Saint George's respiratory questionnaire (SGRQ) -- Impacts Score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Impacts. The Impact score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. |
Baseline (Week 0), Week 4, 12, 26, 40, 52.
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11d_Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) -- at All Study Visits: Activity Score
時間枠：Baseline (Week 0), Week 4, 12, 26, 40, 52.
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Saint George's respiratory questionnaire (SGRQ) -- Activity score. SGRQ is a questionnaire developed to measure health in chronic airflow limitation. SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52). Result show the Saint George's Respiratory Questionnaire (SGRQ) as change from baseline for the domain Activity. The Activity score is calculated on a scale of 0 to 100. A score of 0 indicates no impairment (best health); a score of 100 indicates the worst possible health status. |
Baseline (Week 0), Week 4, 12, 26, 40, 52.
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12_Number of Participants With Saint George's Respiratory Questionnaire (SGRQ) Response (Change From Baseline in Total Score ≤-4) -- at Week 26 and Week 52
時間枠：Baseline (Week 0), Week 26, Week 52.
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Number of participants with Saint George's Respiratory Questionnaire (SGRQ) response, defined as a change from baseline in SGRQ total score ≤ -4, at Week 26 and Week 52. If the change from baseline was > -4, the patient was assessed as a non-responder in terms of SGRQ. Patients with missing change from baseline at the pre-specified tested time points were also classified as non-responders. Results shown represent the number of responder participants in terms of SGRQ, for the comparison of CHF 5993 pMDI versus CHF 1535 pMDI. |
Baseline (Week 0), Week 26, Week 52.
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13a_Change From Baseline for Percentage of Days Without Intake of Rescue Medication -- Over Entire Treatment Period (52 Weeks of Treatment)
時間枠：Baseline (Week 0) to Week 4, 12, 26, 40, 52.
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Days WITHOUT intake of rescue medication. Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the percentage of days without intake of rescue medication. |
Baseline (Week 0) to Week 4, 12, 26, 40, 52.
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13b_Change From Baseline for the Average Use of Rescue Medication -- Over Entire Treatment Period (52 Weeks of Treatment)
時間枠：Baseline (Week 0) to Week 4, 12, 26, 40, 52.
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Average use of rescue medication, over the entire treatment period (52 Weeks of treatment). Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the average use of rescue medication (number of puffs/day). |
Baseline (Week 0) to Week 4, 12, 26, 40, 52.
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14_Rate of Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Rate -- Over Entire Treatment Period (52 Weeks of Treatment)
時間枠：Baseline (Week 0) to Week 52 (entire treatment period).
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Rate of moderate AND severe COPD exacerbations over the entire treatment period of treatment (52 weeks). COPD=Chronic obstructive pulmonary disease |
Baseline (Week 0) to Week 52 (entire treatment period).
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15_First Occurrence of All Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
時間枠：Baseline (Week 0), Week 52.
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First occurrence of at least 1 moderate OR severe COPD exacerbation. First occurrence was analysed by Cox regression as time to first exacerbation and reported as hazard ratio. COPD=Chronic obstructive pulmonary disease |
Baseline (Week 0), Week 52.
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協力者と研究者
捜査官
- 主任研究者：Dave SINGH, MD、University Hospital of South Manchester, MANCHESTER M23 9 QZ, UK
出版物と役立つリンク
一般刊行物
- Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018 Dec 12;13:3971-3981. doi: 10.2147/COPD.S185975. eCollection 2018.
- Singh D, Fabbri LM, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy delays COPD clinically important deterioration vs ICS/LABA, LAMA, or LABA/LAMA. Int J Chron Obstruct Pulmon Dis. 2019 Feb 28;14:531-546. doi: 10.2147/COPD.S196383. eCollection 2019.
- Singh D, Fabbri LM, Corradi M, Georges G, Guasconi A, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy in patients with symptomatic COPD and history of one moderate exacerbation. Eur Respir J. 2019 May 18;53(5):1900235. doi: 10.1183/13993003.00235-2019. Print 2019 May.
- Singh D, Papi A, Corradi M, Pavlisova I, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Vestbo J. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting beta2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016 Sep 3;388(10048):963-73. doi: 10.1016/S0140-6736(16)31354-X. Epub 2016 Sep 1.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (推定)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CCD-1207-PR-0091
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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Beclometasone/Formoterol/Glycopyrrolateの臨床試験
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University of Tennessee Graduate School of MedicineTheravance Biopharma募集
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AstraZeneca完了COPD患者アメリカ, スペイン, ブルガリア, メキシコ, ポーランド, 南アフリカ, ドイツ, アルゼンチン, チリ, チェコ, プエルトリコ