ICS-RECODE Predictors of treatment REsponse to inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease randomised COntrolled trials individual participant Data re-Evaluation

Lead Investigator: Alexander G Mathioudakis, Manchester University NHS Foundation Trust
Title of Proposal Research: ICS-RECODE Predictors of treatment REsponse to inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease randomised COntrolled trials individual participant Data re-Evaluation
Vivli Data Request: 8053
Funding Source: This study will be supported by the NIHR Manchester Biomedical Research Centre (NIHR Manchester BRC). In addition, we have applied for an NIHR HTA grant, to cover the salary of the statistician for 2 years. The University of Manchester will cover the salaries of Dr Alexander G. Mathioudakis, Prof Jørgen Vestbo and Prof Dave Singh.
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Chronic obstructive pulmonary disease, or COPD, affects over 3 million people in the UK. It is a long-term lung condition that makes it difficult to breathe, because the lungs have become damaged. People with COPD experience flare-ups (called exacerbations), that cause poor health and often need treatment in a hospital. As a result, COPD can cause early death and a huge reduction in quality of life.
Some people with COPD benefit from a treatment called “inhaled steroids”. These can help to ease symptoms, improve quality of life, prevent flare-ups, and prolong life. However, they also cause side effects like pneumonia (severe chest infection) and osteoporosis (bone thinning). For this reason, we should only offer inhaled steroids to specific people who will gain the most benefit at a low risk of side effects; this is sometimes called “personalised medicine”. The National Institute for Health and Care Excellence (NICE) recently requested further research to find the best tests to help us identify people who will benefit from inhaled steroids.
Aim: To find out which are the best tests to help us personalise the use of inhaled steroids. We will use data from existing research studies (“clinical trials”) about inhaled steroids in people with COPD.
Design: Many clinical trials have assessed whether inhaled steroids are safe and effective for people with COPD. However, most studies are not big enough to identify the specific characteristics that make a person more or less likely to benefit from inhaled steroids. To overcome this problem, we will collect anonymous information about all the individual people in these trials and combine the results together. Clinical trials are the best source of information for our study because they collect very detailed information about the people who take part. We are confident that by combining so much information we will find an effective test.

We have already performed a thorough search to find all clinical trials that assessed inhaled steroids for COPD. We are now requesting to gain access to the information from all these trials. Once we gain access to data from all these trials, we will first check the results carefully. We will change all the data into a similar format so that we can combine the results. We will assess if the trials were done properly. We will use a cutting edge and complex statistical method to analyse all the data together. This method is called individual participant data (IPD) meta-analysis. We will focus on finding tests that can help us personalise the use of inhaled steroids.
It is very complex to access, merge and analyse all data together. It needs commitment, time and skills. If it is not done properly, it could easily reach wrong conclusions. For this reason, we have brought together a group of experts in COPD, clinical trials, statistics, and IPD meta-analyses. It will take us 2 years to fully process and analyse the data.
Patient and public involvement (PPI): The views of people who are living with COPD are central to our work. For this reason, we included a patient advocate and our PPI lead to join our group. We will involve more patients and other stakeholders in an advisory group. The lay advisory group members will deliver patients’ perspectives on the analyses throughout the study. Upon completion of the analyses, we will organise a focus group with COPD patients, to inform the next steps of our research.

Requested Studies:
A Clinical Outcomes Study to Compare the Effect of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg With Placebo on Survival in Subjects With Moderate Chronic Obstructive Pulmonary Disease (COPD) and a History of or at Increased Risk for Cardiovascular Disease
Data Contributor: GlaxoSmithKline
Study ID: NCT01313676
Sponsor ID: HZC113782

A Randomised, Double-blind, Active-controlled Study to Evaluate the Impact of Stepwise Withdrawal of Inhaled Corticosteroid Treatment in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD) on Optimized Bronchodilator Therapy
Data Contributor: Boehringer Ingelheim
Study ID: NCT00975195
Sponsor ID: 352.2046

A Multicentre, Randomised, Double-blind, Parallel Group, Placebo-controlled Study to Investigate the Long-term Effects of Salmeterol/Fluticasone Propionate (Seretide tm) 50/500mcg BD, Salmeterol 50mcg BD and Fluticasone Propionate 500mcg BD, All Delivered Via the Diskus tm/Accuhaler tm Inhaler, on Mortality and Morbidity of Subjects With Chronic Obstructive Pulmonary Disease (COPD) Over 3 Years of Treatment
Data Contributor: GlaxoSmithKline
Study ID: NCT00268216
Sponsor ID: SCO30003

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).
Data Contributor: GlaxoSmithKline
Study ID: FLTA3025
Sponsor ID: FLTA3025

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)
Data Contributor: GlaxoSmithKline
Study ID: NCT01054885
Sponsor ID: 112207

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.
Data Contributor: GlaxoSmithKline
Study ID: SFCA3007
Sponsor ID: SFCA3007

A Randomized, Double-Blind, Parallel Group, 52-Week Study to Compare the Effect of 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
Study ID: NCT00115492
Sponsor ID: SCO100250
Data Contributor: GlaxoSmithKline

A Randomized, Double-Blind, Parallel Group, 52-Week Study to Compare the Effect of Fluticasone Propionate/Salmeterol DISKUS® Inhaler Combination Product 250/50mcg Twice Daily With Salmeterol DISKUS® Inhaler 50mcg Twice Daily on the Annual Rate of Moderate/Severe Exacerbations in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: GlaxoSmithKline
Study ID: NCT00144911
Sponsor ID: SCO40043

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)
Data Contributor: GlaxoSmithKline
Study ID: NCT01053988
Sponsor ID: 112206

A 12-Week Study to Evaluate the Efficacy and Safety of Fluticasone Furoate/Vilanterol Inhalation Powder (FF/VI) 100/25 mcg Once Daily Compared With Vilanterol Inhalation Powder (VI) 25 mcg Once Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: GlaxoSmithKline
Study ID: NCT02105974
Sponsor ID: 200820

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)
Data Contributor: GlaxoSmithKline
Study ID: NCT01009463
Sponsor ID: 102871

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)
Data Contributor: GlaxoSmithKline
Study ID: NCT01017952
Sponsor ID: 102970

A Randomized, Double-Blind, Parallel Group, Multicenter Study of the Effects of Fluticasone Propionate/Salmeterol Combination Product 250/50mcg BID (ADVAIR DISKUS™) in Comparison to Salmeterol 50mcg BID (SEREVENT DISKUS™) on the Rate of Exacerbations of COPD Following Hospitalization
Data Contributor: GlaxoSmithKline
Study ID: NCT01110200
Sponsor ID: ADC113874

A multicentre, double-blind, placebo-controlled, parallel group study of the efficacy and tolerability of long-term inhaled fluticasone propionate 500mg twice daily via a Volumatic Spacer device in patients with non-asthmatic chronic obstructive pulmonary disease
Data Contributor: GlaxoSmithKline
Study ID: FLTB3054 (FLIT78) [ISOLDE] Sponsor ID: FLTB3054 (FLIT78) [ISOLDE]

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.
Data Contributor: GlaxoSmithKline
Study ID: SFCB3024
Sponsor ID: SFCB3024

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.
Data Contributor: GlaxoSmithKline
Study ID: SFCA3006
Sponsor ID: SFCA3006

Efficacy and Safety Study of Symbicort® Turbuhaler® Versus Oxis® Turbuhaler® in Chronic Obstructive Pulmonary Disease (COPD) Patients (SUMIRE)
Data Contributor: AstraZeneca
Study ID: NCT01069289
Sponsor ID: N/A

A Comparison of SYMBICORT® pMDI With Formoterol Turbuhaler® in Subjects With COPD
Data Contributor: AstraZeneca
Study ID: NCT00419744
Sponsor ID: N/A

Comparing the Efficacy of Symbicort® pMDI and Formoterol Turbuhaler in Reducing Exacerbations in Patients With Cronic Obstructive Pulmonary Disease (RISE)
Data Contributor: AstraZeneca
Study ID: NCT02157935
Sponsor ID: N/A

We will seek additional studies comparing ICS versus no ICS directly by other Pharma companies (Aventis, Chiesi, Novartis, Merck, Mundipharma and Schering-Plough) that will be analysed separately, in line with those Pharma companies policies.
Data Contributor: I WILL BRING MY OWN
Study ID: N/A
Sponsor ID: N/A

A Phase III, 52 Week, Randomized, Double-blind, 3-arm Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI With the Fixed Dose Dual Combinations of FF/VI and UMEC/VI, All Administered Once-daily in the Morning Via a Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease
Data Contributor: GlaxoSmithKline
Study ID: NCT02164513
Sponsor ID: CTT116855