Treatment and Exacerbation in COPD Subjects

NCT ID: NCT03375450

Last Updated: 2020-09-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

60243 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-06-09

Study Completion Date

2019-08-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Comparative Effectiveness Study

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Observation

Cohort of patients with COPD

Standard of Care

Intervention Type OTHER

Participants will be followed as per local routine primary healthcare practice

Interventions

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Standard of Care

Participants will be followed as per local routine primary healthcare practice

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

\- All adult COPD patients aged ≥40, with a smoking history, incident prescription of a study therapy, and research acceptable data.

Exclusion Criteria

\- Any subjects with less than 12 months of UTS data prior to index date.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

London, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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D589BR00039

Identifier Type: -

Identifier Source: org_study_id

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