Ignite Creation Date:
2024-05-06 @ 1:14 AM
Last Modification Date:
2024-10-26 @ 11:01 AM
Study NCT ID:
NCT01763463
Status:
COMPLETED
Last Update Posted:
2015-03-11
First Post:
2012-08-23
Brief Title:
WEUSKOP6416 Evaluating Pneumonia in Chronic Obstructive Pulmonary Disease COPD Subjects
Sponsor:
GlaxoSmithKline
Organization:
GlaxoSmithKline
Study Overview
Official Title:
WEUSKOP6416 Evaluating Serious Pneumonia in Subjects With Chronic Obstructive Pulmonary Disease COPD to Inform Risk Minimization A Retrospective Observational Study
Status:
COMPLETED
Status Verified Date:
2015-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Pneumonia remains an important cause of morbidity and mortality in older adults with obstructive lung disease Risk factors for pneumonia including episodes associated with a hospital admission have been extensively characterized in clinical trials and observational studies of patients with COPD and include older age lower predicted FEV1 50 prior COPD exacerbations dyspnea normal to low body mass index 25 current smoking and certain co-morbid conditions eg dementia The use of inhaled corticosteroids ICS has also been identified as associated with an increased risk of pneumonia in patients with COPD
The primary objective of this study is to estimate the magnitude of known risk factors and the outcomes of pneumonia requiring hospitalization and the potential effect modification of these risk factors by ICS use The primary endpoints will be severe pneumonia defined as community-acquired pneumonia CAP resulting in hospitalization andor death and hospital-acquired pneumonia HAP diagnosed after two days in the hospital As a secondary endpoint CAP that did not result in hospitalization or death will be examined As a secondary objective we will describe characteristics for those patients who develop pneumonia requiring hospitalization compared to those with pneumonia not requiring admission
This study will use the General Practice Online Database GOLD formerly referred to as the General Practice research Database GPRD a primary care electronic medical record database
A new user cohort will be defined among patients with COPD who are 45 years and older in the United Kingdom Patients will be considered a new user of ICS-containing medications if they had not received a prescription for an ICS-containing medication in the prior year The comparator treatment group will be new users of long-acting bronchodilators LABD including long-acting beta-agonists LABA or long-acting antimuscarinics LAMA In the one year washout period all new users could not have either ICS-containing medications or LABD
Prior to conducting the analysis feasibility analyses will be conducted to evaluate of the number of pneumonia events and the number of new users separately to examine the available precision based on the study design
Patients will be followed from the date of their first eligible prescription Cohort Entry Date until the earliest of the following date of study end point first pneumonia event of interest date of treatment end up to 60-day gap allowed for each inhaler date of transfer to a new practice date of ICS initiation among LABD new users death or study end end of available data As part of the primary analysis patients will be examined for their first severe pneumonia severe CAP HAP As a secondary analysis time to non-severe CAP will be examined Incidence rates of the pneumonia outcomes will be calculated as the number of patients experiencing an event divided by the person-years at risk
Multivariable analysis will be performed using Cox proportional hazard model with adjustment for confounders and medication exposure To adjust for differences confounding by severity due to differences in prescribing between ICS-containing medications and LABD propensity scores PS will be utilized using inverse probability of treatment weighting IPTW The propensity score will be estimated to model the probability of a patient receiving ICS-containing medication prescription versus receiving a LABD prescription given a patients observed set of baseline covariates
Effect modification statistical interaction will be evaluated based on available theory and include ICS medication use by known risk factors for pneumonia BMI21 BMI 21-249 BMI 25 age GOLD stage IIIIV MRC dyspnea score 4 history of pneumonia diagnosis current smoking status social deprivation quartiles Additional interactions may be evaluated
To test proportionality of the hazard functions model diagnostics will be performed
To compare severe pneumonia with non-severe pneumonia in patients with COPD characteristics of patients experiencing non-severe CAP vs severe CAP or HAP will be tabulated To assess differences between treatments clinical and patient characteristics will be compared using the chi-square tests or Wilcoxon tests for categorical or continuous data respectively Severe CAP and HAP may be combined Modeling of clinical and patient characteristics may be considered using logistic regression using CAP vs severe CAP and then with severe CAP vs HAP
Additional analysis or adjustments to the analytic or modeling strategy will be performed if the data warrants A more detailed modeling strategy including generation of the propensity scores and Cox modeling will be created in a separate analysis plan Adjustments to the a priori plan will be described in the final study report
The primary objective of this study is to estimate the magnitude of known risk factors and the outcomes of pneumonia requiring hospitalization and the potential effect modification of these risk factors by ICS use The primary endpoints will be severe pneumonia defined as community-acquired pneumonia CAP resulting in hospitalization andor death and hospital-acquired pneumonia HAP diagnosed after two days in the hospital As a secondary endpoint CAP that did not result in hospitalization or death will be examined As a secondary objective we will describe characteristics for those patients who develop pneumonia requiring hospitalization compared to those with pneumonia not requiring admission
This study will use the General Practice Online Database GOLD formerly referred to as the General Practice research Database GPRD a primary care electronic medical record database
A new user cohort will be defined among patients with COPD who are 45 years and older in the United Kingdom Patients will be considered a new user of ICS-containing medications if they had not received a prescription for an ICS-containing medication in the prior year The comparator treatment group will be new users of long-acting bronchodilators LABD including long-acting beta-agonists LABA or long-acting antimuscarinics LAMA In the one year washout period all new users could not have either ICS-containing medications or LABD
Prior to conducting the analysis feasibility analyses will be conducted to evaluate of the number of pneumonia events and the number of new users separately to examine the available precision based on the study design
Patients will be followed from the date of their first eligible prescription Cohort Entry Date until the earliest of the following date of study end point first pneumonia event of interest date of treatment end up to 60-day gap allowed for each inhaler date of transfer to a new practice date of ICS initiation among LABD new users death or study end end of available data As part of the primary analysis patients will be examined for their first severe pneumonia severe CAP HAP As a secondary analysis time to non-severe CAP will be examined Incidence rates of the pneumonia outcomes will be calculated as the number of patients experiencing an event divided by the person-years at risk
Multivariable analysis will be performed using Cox proportional hazard model with adjustment for confounders and medication exposure To adjust for differences confounding by severity due to differences in prescribing between ICS-containing medications and LABD propensity scores PS will be utilized using inverse probability of treatment weighting IPTW The propensity score will be estimated to model the probability of a patient receiving ICS-containing medication prescription versus receiving a LABD prescription given a patients observed set of baseline covariates
Effect modification statistical interaction will be evaluated based on available theory and include ICS medication use by known risk factors for pneumonia BMI21 BMI 21-249 BMI 25 age GOLD stage IIIIV MRC dyspnea score 4 history of pneumonia diagnosis current smoking status social deprivation quartiles Additional interactions may be evaluated
To test proportionality of the hazard functions model diagnostics will be performed
To compare severe pneumonia with non-severe pneumonia in patients with COPD characteristics of patients experiencing non-severe CAP vs severe CAP or HAP will be tabulated To assess differences between treatments clinical and patient characteristics will be compared using the chi-square tests or Wilcoxon tests for categorical or continuous data respectively Severe CAP and HAP may be combined Modeling of clinical and patient characteristics may be considered using logistic regression using CAP vs severe CAP and then with severe CAP vs HAP
Additional analysis or adjustments to the analytic or modeling strategy will be performed if the data warrants A more detailed modeling strategy including generation of the propensity scores and Cox modeling will be created in a separate analysis plan Adjustments to the a priori plan will be described in the final study report
Detailed Description:
Advantages of the primary care database include the ability to link to secondary care Hospital Episode Statistics HES and to examine risk factors for pneumonia included in the UK Quality Outcomes Framework for COPD that are not collected routinely in most other observational healthcare data sources eg BMI lung function smoking history MRC dyspnea score Another advantage of this study is the new-user design as it minimizes biases that can be caused by alternative designs which compare events between prevalent user groups eg survivor bias covariates altered by prior exposure
There are also known limitations of observational database analyses where treatments are not randomized including the potential for confounding by severity that may not be fully accounted for in the analysis ICS-containing medications may be dispensed to patients who have more severe COPD than patients who are receiving long-acting bronchodilators alone In this study we will adjust for disease severity and patient characteristics in the period prior to initiation using propensity scores Medication use in CPRD-GOLD is based on prescribed medications recorded by the primary care physician which might not have been dispensed at the pharmacy or ultimately utilized by the patient Finally diagnostic practices for pneumonia may be different in the UK compared with other countries limiting the generalizability
As with any outcome of interest identifying pneumonia in databases is imperfect and there may be confusion between diagnoses of pneumonia and influenza or serious exacerbation To our knowledge the relationship between pneumonia recorded in these primary and secondary care databases have not been investigated In addition there is lack of agreement between pneumonia classification in the absence of chest x-rays sputum etc
Despite the limitations this study will provide insights into risk factors for serious pneumonia including whether ICS modify the effect of established risk factors for serious pneumonia The results may identify specific patient groups that are at greatest risk of serious pneumonia and may identify where risk minimization andor medical recommendations may be appropriate
There are also known limitations of observational database analyses where treatments are not randomized including the potential for confounding by severity that may not be fully accounted for in the analysis ICS-containing medications may be dispensed to patients who have more severe COPD than patients who are receiving long-acting bronchodilators alone In this study we will adjust for disease severity and patient characteristics in the period prior to initiation using propensity scores Medication use in CPRD-GOLD is based on prescribed medications recorded by the primary care physician which might not have been dispensed at the pharmacy or ultimately utilized by the patient Finally diagnostic practices for pneumonia may be different in the UK compared with other countries limiting the generalizability
As with any outcome of interest identifying pneumonia in databases is imperfect and there may be confusion between diagnoses of pneumonia and influenza or serious exacerbation To our knowledge the relationship between pneumonia recorded in these primary and secondary care databases have not been investigated In addition there is lack of agreement between pneumonia classification in the absence of chest x-rays sputum etc
Despite the limitations this study will provide insights into risk factors for serious pneumonia including whether ICS modify the effect of established risk factors for serious pneumonia The results may identify specific patient groups that are at greatest risk of serious pneumonia and may identify where risk minimization andor medical recommendations may be appropriate
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| WEUSKOP6416 | OTHER | GSK | None |