Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03375450 |
| Other study ID # |
D589BR00039 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 9, 2017 |
| Est. completion date |
August 30, 2019 |
Study information
| Verified date |
September 2020 |
| Source |
AstraZeneca |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This is a study comparing the effects of ICS containing treatments in patients with chronic
obstructive pulmonary disease (COPD) in a real world setting, using the UK Clinical Practice
Research Datalink (CPRD) linked with Hospital Episode Statistics (HES). The main outcome to
be assessed is exacerbation rates.
Description:
Background/Rationale:
For people with chronic obstructive pulmonary disease (COPD), standard maintenance inhaler
treatments consist of inhaled corticosteroids (ICS) and long acting bronchodilators
(principal classes include long-acting beta-2-agonists (LABAs) and long-acting muscarinic
antagonists (LAMAs)). Clinical trials indicate that adding ICS to treatment combinations may
provide rapid and sustained improvements (1). However, ICS may be associated with adverse
effects, notably pneumonia.
There is a need for real-world effectiveness data regarding COPD treatment in order to
demonstrate that improvements in lung function translate into reductions in exacerbations,
hospitalizations or morbidity.
Objectives and Hypotheses: We hypothesize that ICS containing treatment regimens (including
triple therapy - ICS/LABA/LAMA) are more effective at preventing AECOPD than non-ICS
containing regimens. The main objective is to assess the impact of ICS therapy on
exacerbation outcomes in a COPD population and identify which patient subgroups may achieve
the greatest benefit.
Methods:
Study design: Cohort study examining comparative effectiveness
Data Source(s): Clinical Practice Research Datalink (CPRD) GOLD, Hospital Episode Statistics
(HES) and Office for National Statistics (ONS) mortality data
Study Population: Patients ≥40 years-old, with a validated diagnosis of COPD registered
between the 1st of January 2006 and the 29 February 2016. Eligible patients must have a
smoking history, data recorded at least 12 months prior to the study index date and have
Up-To-Standard (UTS) data as defined by CPRD.
Exposure(s): ICS containing (LAMA/LABA/ICS and LABA/ICS) regimens and non-ICS containing
regimens (LABA/LAMA, LAMA monotherapy).
Outcome(s): Exacerbationsmof COPD, defined using a published algorithm, both GP treated and
hospitalised(2), hospitalised pneumonias.
Sample Size Estimations:
A two-sample log-rank test for power indicated that a total of n=2,858 patients (1,429
patients per group) will be required to detect a 15% risk reduction for exacerbation in the
triple therapy population compared to the dual-therapy group (comparison which requires the
maximum number of patients). This is based on a 60% annual hazard rate for exacerbation in
the dual-therapy population and a 51% annual hazard rate for exacerbation in the triple
therapy group; assuming power of 90%, alpha=0.05, and a conservative accrual period of one
year and a minimum follow-up time of one year.
Statistical Analysis: Descriptive statistics will be used to characterize patients according
to baseline demographic, clinical and treatment factors and to study treatment patterns
during follow-up.
Analytical statistics will estimate time to exacerbation events per treatment type during the
follow-up period. These statistics will include extended Cox regression models, marginal
structural models (MSM) and inverse probability weighting (IPW).
Sensitivity analyses will assess follow-up time in incremental periods in order to examine
the impact of drug type and drug changes over time. We will also analyse associations between
demographic and clinical factors and treatment received.
