Response to placebo in patients with chronic obstructive pulmonary disease

Lead Investigator: Surya Bhatt, RespirAnalytics LLC
Title of Proposal Research: Response to placebo in patients with chronic obstructive pulmonary disease
Vivli Data Request: 10487
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Chronic obstructive pulmonary disease (COPD) is the name for a group of lung conditions that resulted in shortness of breath and long-term cough. COPD is a broad term that includes emphysema (damage to the air sacs in the lungs) and chronic bronchitis (long-term inflammation of the airways). COPD is most associated with cigarette smoking, but it is increasingly recognized that people who have never smoked can also develop COPD. It most commonly affects middle-aged or older adults. COPD does not have any cure, and treatment is mostly aimed at decreasing symptom burden. Treatment involves prescribing inhalers that are bronchodilators (medications that open up the airways and hence ease breathing) and inhaled corticosteroids (medications which decrease inflammation in the lungs).

Current treatment with inhaled long-acting bronchodilators and inhaled corticosteroids result in improvement in shortness of breath, flareups or exacerbations (worsening of symptoms), and quality of life. They also result in improvement in lung function. In clinical trials, these medications are compared with the effect of an inactive medication or placebo for the improvement of lung function, shortness of breath, and quality of life. Quality of life is frequently measured in clinical trials using the St. George’s Respiratory Questionnaire (SGRQ) score. The SGRQ is a survey designed to measure the impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. The scale ranges from 1 to 100, where 0 indicates best health and 100 indicates worst health.

A reduction in the SGRQ score by at least 4 points is considered perceivable by patients and hence clinically meaningful. In clinical studies, approximately 55% of individuals prescribed these inhalers report a significant improvement in quality of life. It should however be noted that approximately 40% of individuals given inactive medication or placebo also report a significant improvement in quality of life.

These differences in the proportion of individuals who respond to these medications versus placebo can be used for calculating how many individuals should be enrolled in future clinical trials. Prior studies indicate that patients with milder disease (and thereby a lower SGRQ score) have a greater response to inhaled COPD medications than those with more severe disease. Whether individuals receiving the inactive medication or placebo respond differently depending on disease severity or symptom burden is not known. This study will look at whether the proportion of individuals who show a response in SGRQ will differ by disease severity within the placebo group as well. The analysis will include individuals enrolled in prior trials of bronchodilators and inhaled corticosteroid therapies.

Our findings could impact how future clinical trials are set up. For example, if patients with more serious illnesses or milder symptoms react very differently to a placebo, this needs to be considered in trials to accurately measure how well actual treatments work.

Requested Studies:

A Randomized, Double Blind, Chronic Dosing, Placebo-Controlled, Parallel Group, Multi Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo and Spiriva® Handihaler® (Tiotropium Bromide 18 µg Open-Label) as an Active Control
Data Contributor: AstraZeneca
Study ID: NCT01854645
Sponsor ID: PT003006

Efficacy {FEV1, COPD Exacerbations & HRQoL} & Safety of 5mcg Tiotropium Respimat in COPD
Data Contributor: Boehringer Ingelheim
Study ID: NCT00387088
Sponsor ID: 205.372

A Randomized, Double-blind, Placebo-controlled, Parallel Group Trial Assessing the Rate of Decline of Lung Function With Tiotropium 18 mcg Inhalation Capsule Once Daily in Patients With Chronic Obstructive Pulmonary Disease (COPD).
Data Contributor: Boehringer Ingelheim
Study ID: NCT00144339
Sponsor ID: 205.235

A Multiple Dose Comparison of Tiotropium Inhalation Capsules, Salmeterol Inhalation Aerosol and Placebo in a Six-Month, Double-Blind, Double-Dummy, Safety and Efficacy Study in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT02172287
Sponsor ID: 205.130

A Randomized, Double-blind, Double-dummy, Placebo- and Active-controlled, Parallel Group Efficacy and Safety Comparison of 12-week Treatment of Two Doses (5 Mcg and 10 Mcg) of Tiotropium Inhalation Solution Delivered by the Respimat Inhaler, Placebo and Ipratropium Bromide Inhalation Aerosol (MDI) i
Data Contributor: Boehringer Ingelheim
Study ID: NCT00240435
Sponsor ID: 205.252

A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Comparison of One-Year Treatment of Two Doses (5mg and 10mg) of Tiotropium Inhalation Solution Delivered by the Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00168831
Sponsor ID: 205.255

A Randomised, Double-blind, Placebo- and Active-controlled Parallel Group Study to Assess the Efficacy of 12 Weeks of Once Daily Treatment of Two Doses of Orally Inhaled Tiotropium+ Olodaterol Fixed Dose Combination (Delivered by the Respimat Inhaler) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT02006732
Sponsor ID: 1237.26

A Randomised, Double-blind, Placebo- and Active-controlled Parallel Group Study to Assess the Efficacy of 12 Weeks of Once Daily Treatment of Two Doses of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (Delivered by the Respimat Inhaler) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT01964352
Sponsor ID: 1237.25

Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 mcg [2 Actuations of 2.5 mcg] and 10 mcg [2 Actuations of 5 mcg]) Delivered by the Respimat® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00782509
Sponsor ID: 1222.12

A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 ug] and 10 ug [2 Actuations of 5 ug]) Delivered by the Respimat® Inhaler, and 48 Weeks of Twice Daily Foradil® (12 µg) Delivered by the Aerolizer® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00796653
Sponsor ID: 1222.14

A Randomised, Double-Blind, Double-Dummy, Placebo- and Active-Controlled, Parallel Group Efficacy and Safety Comparison of 12-Week Treatment of Two Doses [5 μg (2 Actuations of 2.5 μg) and 10 μg (2 Actuations of 5 μg)] of Tiotropium Inhalation Solution Delivered by the Respimat Inhaler, Placebo and Ipratropium Bromide Inhalation Aerosol (MDI) in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Data Contributor: Boehringer Ingelheim
Study ID: NCT00239473
Sponsor ID: 205.251