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Proposal 999

Title of the Proposed Research

Assessing the Comparative Efficacy of Therapeutics for Chronic Obstructive Pulmonary Disease (COPD): A Meta-Analysis of Randomized Trials

Lead Researcher

Kristen M Sweet

Affiliation

Thomson Reuters

Funding Source

None

Potential Conflicts of Interest

None

Data Sharing Agreement Date

17 June 2015

Lay Summary

In 2011, the third leading cause of death in the United States was attributed to Chronic Obstructive Pulmonary Disease (COPD) and other chronic lower respiratory diseases (Hoyert DL, Natl Vital Stat Rep, 2012). While greater than 10 million adults in the US have reportedly been diagnosed with COPD diseases including emphysema, chronic bronchitis, refractory asthma, and bronchiectasis in 2000, this number is likely under-reported and estimated to be closer to 24 million Americans (Centers for Disease Control and Prevention. MMWR. 2002). This indicates a need for better diagnosis of COPD, as well as better treatment options for those diagnosed.

The development of drugs targeting COPD is a major focus of the pharmaceutical industry today. The estimated direct medical cost for COPD was $14.7 billion in 2003, with an additional $9.2 billion associated with indirect costs associated with the disease (Sullivan SD, Chest, 2000). Despite numerous treatment options, researchers continue to seek a more effective therapeutic with fewer side effects.

Recent clinical trials have tested the efficacy and safety of corticosteroids, anticholinergic/ muscarinic cholinergic receptors, bronchodilators, and long acting beta2 agonists individually or in combination in patients with COPD. These drugs are proposed to function via different mechanisms to alleviate symptoms of COPD. Thus, ongoing research aims to understand the efficacy of these drugs independently as well as in combination to achieve an additive effect.

In this study, we aim to perform meta-analysis on COPD drugs with available data from recent Phase 2 and 3 clinical trials. The goal of this analysis is to 1) better understand the population of COPD patients at baseline. Since COPD is underdiagnosed, the first objective is to characterize the baseline features of disease. We then aim to 2) use data from these studies to assess efficacy of these drugs on alleviating symptoms of COPD. 3) By analyzing data across studies, we aim to determine if patients can be stratified to treatment based on baseline information and study results. By understanding how different patient populations respond to different treatments, this would result in better standard of care for patients suffering from COPD.

In order to perform the proposed analyses, we will utilize tranSMART v.1.2. TranSMART is an open-source data warehouse platform with analysis capabilities for a single study as well as cross-trial. Using tranSMART will enable us to perform detailed analysis of clinical and molecular data from ClinicalStudyDataRequest.com to better understand COPD and how patients respond to tested therapies.

Study Data Provided

Study GSK-AC2108378: A randomised, double-blind, placebo-controlled, dose ascending, 2-cohort, parallel group study to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of twice-daily inhaled doses of GSK233705B formulated with the excipient Magnesium Stearate in COPD subjects for 7-days.
Study GSK-AC2110664: Dose-Ranging Study for GSK233705B Delivered Once Daily in Subjects with COPD
Study GSK-DB1111581: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, 4-week study to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of repeat inhaled doses of the combination of GSK233705 and GW642444 administered once-daily in subjects with COPD
Study GSK-HZC102871: HZC102871: A 52-week efficacy and safety study to compare the effect of three dosage strengths of Fluticasone Furoate/GW642444 Inhalation Powder with GW642444 on the Annual Rate of Exacerbations in Subjects with Chronic Obstructive Pulmonary Disease (COPD)
Study GSK-HZC112206: A 24-Week Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder and the Individual Components Delivered Once Daily (AM) Via a Novel Dry Powder Inhaler Compared with Placebo in Subjects with Chronic Obstructive Pulmonary Disease (COPD)
Study GSK-HZC112207: A 24-Week Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder and the Individual Components Delivered Once Daily (AM) Via a Novel Dry Powder Inhaler Compared with Placebo in Subjects with Chronic Obstructive Pulmonary Disease (COPD)
Study GSK-HZC113107: A 12-week study to evaluate the 24 hour pulmonary function of Fluticasone Furoate (FF)/Vilanterol Inhalation Powder (FF/VI Inhalation Powder) once daily compared with Salmeterol/Fluticasone Propionate (FP) Inhalation Powder twice daily in subjects with Chronic Obstructive Pulmonary Disease (COPD)
Study GSK-FLTA3025: A randomized, double-blind, parallel-group, comparative trial of inhaled fluticasone propionate 250mcg twice daily, 500mcg twice daily, and placebo twice daily via the DISKUS® inhaler in subjects with chronic obstructive pulmonary disease (COPD).
Study GSK-HZC102970: HZC102970: A 52-week efficacy and safety study to compare the effect of three dosage strengths of Fluticasone Furoate/GW642444 Inhalation Powder with GW642444 on the Annual Rate of Exacerbations in Subjects with Chronic Obstructive Pulmonary Disease (COPD)
Study GSK-SCO30003: A multicentre, randomised, double-blind, parallel group, placebo-controlled study to investigate the long-term effects of salmeterol/fluticasone propionate (SERETIDE® inhaler) 50/500mcg BD, salmeterol 50mcg BD and fluticasone propionate 500mcg BD, all delivered via the DISKUS®/ACCUHALER® inhaler, on mortality and morbidity of subjects with chronic obstructive pulmonary disease (COPD) over 3 years of treatment
Study GSK-SCO30005: A 13-week, double-blind, parallel group, multi-centre study to compare the bronchial anti-inflammatory activity of the combination of salmeterol/fluticasone propionate 50/500mcg twice daily compared with placebo twice daily in patients with Chronic Obstructive Pulmonary Disease (COPD)
Study GSK-SFCB3024: A multicentre, randomised, double-blind, parallel group study to compare the efficacy and safety of the Salmeterol/Fluticasone combination product (50/500mg strength) twice daily with Salmeterol 50mg twice daily alone and Fluticasone Propionate 500mg twice daily alone, all delivered via the Diskus/Accuhaler inhaler, in the treatment of patients with chronic obstructive pulmonary disease.
Study GSK-SFCA3007: A randomized, double-blind, placebo-controlled, parallel-group, trial evaluating the safety and efficacy of the Diskus formulation of salmeterol 50mcg twice daily and fluticasone propionate 250mcg twice daily individually and in combination as compared to placebo in COPD patients.
Study GSK-SFCA3006: A randomized, double-blind, placebo-controlled, parallel-group, trial evaluating the safety and efficacy of the Diskus formulations of salmeterol 50mcg twice daily and fluticasone propionate 500mcg twice daily individually and in combination as compared to placebo in COPD patients.
Study GSK-SCO100470: A multicentre, randomised, double-blind, parallel group, 24 week study to compare the effect of salmeterol/fluticasone propionate combination product 50/250mcg, with salmeterol 50mcg both delivered twice daily via DISKUS®/ACCUHALER® inhaler on lung function and dyspnoea in subjects with Chronic Obstructive Pulmonary Disease (COPD).A multicentre, randomised, double-blind, parallel group, 24 week study to compare the effect of salmeterol/fluticasone propionate combination product 50/250mcg, with salmeterol 50mcg both delivered twice daily via DISKUS®/ACCUHALER® inhaler on lung function and dyspnoea in subjects with Chronic Obstructive Pulmonary Disease (COPD).
Study GSK-SCO30002: A multicentre randomised double-blind parallel group placebo controlled study assessing the efficacy and safety of inhaled salmeterol/fluticasone 50/500mcg twice daily, inhaled fluticasone 500mcg twice daily and placebo all administered via MDI in the treatment of patients with COPD
Study GSK-SLGA4005: A Randomized, Double-Blind, Double-Dummy, Comparative Clinical Trial of 12-Week Courses of Salmeterol Xinafoate Versus Ipratropium Bromide Versus Placebo (PRN Ventolin®) in Subjects With Chronic Obstructive Pulmonary Disease
Study GSK-SLGA4004: A Randomized, Double-blind, Double-Dummy, Comparative Clinical Trial of 12-Week Courses of Salmeterol Xinafoate Versus Ipratropium Bromide Versus Placebo (PRN Ventolin) in Subjects With Chronic Obstructive Pulmonary Disease
Study GSK-HZC110946: A three-way incomplete block crossover study to investigate the 24-hour pulmonary function of three dosage strengths of Fluticasone Furoate (FF)/GW642444 Inhalation Powder vs. Placebo, in subjects with Chronic Obstructive Pulmonary Disease (COPD)
Study GSK-HZC111348: Study HZC111348, a repeat-dose study of GW685698/GW642444 Inhalation Powder versus Placebo in the Treatment of Chronic Obstructive Pulmonary Disease (COPD)
Study GSK-SCO104962: A randomised, double-blind, double dummy, 3 way crossover study evaluating the effects of a combination of Seretide 50/500mcg twice daily plus tiotropium bromide 18mcg once daily compared with the individual agents (tiotropium bromide 18mcg alone and Seretide50/500mcg alone) in the treatment of subjects with COPD
Study GSK-DB2113120: Safety, tolerability, pharmacokinetics and pharmacodynamics of the combination of GSK573719 and GW642444 in subjects with COPD
Study GSK-DB2113361: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 Inhalation Powder and the Individual Components Delivered Once-Daily via a Novel Dry Powder Inhaler in Subjects with Chronic Obstructive Pulmonary Disease
Study GSK-DB2113373: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 Inhalation Powder and the Individual Components Delivered Once-Daily via a Novel Dry Powder Inhaler in Subjects with Chronic Obstructive Pulmonary Disease
Study BI-205.235: Evaluation of the Long- Term Effects of Spiriva on Lung Function in COPD Patients

Statistical Analysis Plan

The statistical analysis plan will be added after the research is published.

Publication Citation

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