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Proposal 1640

Title of the Proposed Research

Effect of Fluticasone/Salmeterol on Chronic Bronchitis Symptoms and Associated Patient Reported Outcomes: a post-hoc analysis of the TORCH trial

Lead Researcher

Victor Kim

Affiliation

Lewis Katz School of Medicine, Temple University.

Funding Source

None

Potential Conflicts of Interest

Funded by NHLBI K23HL094696; Chairman, Critical Care Test Writing Committee, American Board of Internal Medicine; Member, Exam Chairs Committee, American Board of Internal Medicine; Advisory boards for Astra Zeneca, Concert Pharmaceuticals, Gala Therapeutics, CSA Medical

Data Sharing Agreement Date

28 February 2017

Lay Summary

Chronic Obstructive Pulmonary Disease (COPD) affects 12-16 million people in the US and is the third leading cause of death worldwide. COPD encompasses a spectrum of diseases, with chronic bronchitis (CB, defined as chronic cough and phlegm production) at one end and emphysema at the other, with most individuals having some characteristics of both. CB affects 3.4-22.0% of all adults, and CB affects anywhere from 14-74% of COPD patients. CB has been shown in numerous studies to increase COPD “flare-ups” (i.e. exacerbations), increase breathlessness, reduce quality of life and physical functioning, and may increase mortality. Despite this, few studies have analyzed the effects of inhaled medications on CB to date.

The TORCH trial randomized patients with COPD to placebo, salmeterol, fluticasone, or fluticasone/salmeterol therapy for three years. The primary endpoint of a decrease in mortality was unfortunately not met, most likely because of a high dropout rate and a less than anticipated level of mortality in the placebo group. The three non-placebo groups did experience improvements in health related quality of life, a reduction in lung function decline, and reduced numbers of exacerbations. However, the study did not classify patients into whether or not they had CB at baseline.

Conceptually, the use of an inhaled corticosteroid (i.e. fluticasone) would decrease symptoms of CB because of its known effects on reducing airway inflammation. This has unfortunately never been shown in a large, randomized controlled trial. Therefore, this analysis of previously collected data is paramount to ascertaining whether fluticasone or fluticasone/salmeterol combination reduces CB symptoms and associated COPD-related outcomes.

We hypothesize that those receiving fluticasone, whether alone or with salmeterol, will have a greater reduction of CB symptoms and exacerbations in those with CB compared to those without CB. Should our hypothesis be correct, it will revolutionize the way physicians treat patients with CB in the era of personalized medicine. To prove this, we propose the following:
1) We will determine which patients in the TORCH trial had CB at study entry using a proven novel definition of CB derived from the Saint George’s Respiratory Questionnaire (SGRQ), a validated measure of COPD health related quality of life. We will ascertain how many patients in each of the four arms of the trial had CB.
2) We will compare the various outcomes between those with and without CB in each arm, in order to see if the treatments had a greater benefit in those with CB. As the SGRQ, lung function, exacerbations, side effects, and mortality were tracked at regular intervals, we will be able to determine the effects of therapy in those with and without CB over the course of three years. Additionally, we will be able to determine if there was a greater reduction in cough and phlegm symptoms in those with CB compared to those without CB.

Study Data Provided

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

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.