Comparative Effectiveness StudyNCT03375450
Treatment and Exacerbation in COPD Subjects
An observational study of Comparative Effectiveness Study, run by AstraZeneca at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Comparative Effectiveness Study
- How many people
- 60,243 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Jun 2017to 30 Aug 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: We will include all patients ≥40 years-old, with a validated diagnosis of COPD (29) recorded between the 1st of January 2006 and 29 Feb 2016 and incident use of one of the therapies under investigation during the study period. 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 (Appendix A lists Read codes for identification and characterization of the COPD population). The COPD definition has been validated in the CPRD against a reference standard of physician review of patient notes by the Imperial College research team. These definitions have high Positive Predictive Value (PPV) \>85%, and will be used in this analysis. All eligible CPRD GOLD patients will be included in the descriptive analysis, regardless of their eligibility for data linkage to HES, ONS and IMD data. The follow-up and analytical statistics will only be applied to patients eligible for linkage.
Who may be able to join
- All adult COPD patients aged ≥40, with a smoking history, incident prescription of a study therapy, and research acceptable data.
Who cannot join
- Any subjects with less than 12 months of UTS data prior to index date.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Retrospective Comparative Effectiveness Study Assessing Treatment and Rates of Exacerbation Among Chronic Obstructive Pulmonary Disease Subjects in England
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.
Read the detailed 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.
- Conditions
- Comparative Effectiveness Study
- Being tested
- Standard of Care
- Keywords
- Epidemiology, Chronic Obstructive Disease, Comparative Effectiveness, Exacerbation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of CareOther
Participants will be followed as per local routine primary healthcare practice
| Study group | Role | What they receive |
|---|---|---|
| Observation | Cohort of patients with COPD Receives: Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Exacerbation
Observational study with 10 year follow-up
Measured: 10 years
Secondary outcomes (1)
Pneumonia
Observational study with a 10 year follow up
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2017
- Study start9 Jun 2017
- Primary completion30 Aug 2019
- Study completion30 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Comparative Effectiveness StudyStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 60,243 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03375450
- Sponsor's protocol ID
- D589BR00039
- Status last verified
- Sep 2020
- First submitted
- 13 Dec 2017
- Last updated
- 14 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrospective Comparative Effectiveness Study Assessing Treatment and Rates of Exacerbation Among Chronic Obstructive Pulmonary Disease Subjects in England
- ClinicalTrials.gov ID
- NCT03375450
- Acronym / sponsor ID
- D589BR00039
- Conditions
- Comparative Effectiveness Study
- Keywords
- Epidemiology, Chronic Obstructive Disease, Comparative Effectiveness, Exacerbation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60,243 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 9 Jun 2017 (actual)
- Primary completion
- 30 Aug 2019 (actual)
- Study completion
- 30 Aug 2019 (actual)
- First posted
- 18 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Observation | – | Other: Standard of CareCohort of patients with COPD |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- We will include all patients ≥40 years-old, with a validated diagnosis of COPD (29) recorded between the 1st of January 2006 and 29 Feb 2016 and incident use of one of the therapies under investigation during the study period. 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 (Appendix A lists Read codes for identification and characterization of the COPD population). The COPD definition has been validated in the CPRD against a reference standard of physician review of patient notes by the Imperial College research team. These definitions have high Positive Predictive Value (PPV) \>85%, and will be used in this analysis. All eligible CPRD GOLD patients will be included in the descriptive analysis, regardless of their eligibility for data linkage to HES, ONS and IMD data. The follow-up and analytical statistics will only be applied to patients eligible for linkage.
Key inclusion criteria (1 listed)
- All adult COPD patients aged ≥40, with a smoking history, incident prescription of a study therapy, and research acceptable data.
Key exclusion criteria (1 listed)
- Any subjects with less than 12 months of UTS data prior to index date.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of CareParticipants will be followed as per local routine primary healthcare practice | Other | Observation |
Primary outcome
Acute Exacerbation
Time frame: 10 years
Observational study with 10 year follow-up
1 secondary outcome
Pneumonia
Time frame: 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2020.
- CSR SynopsisLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Comparative Effectiveness Study, run by AstraZeneca at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute Exacerbation (time frame: 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2020.