Aclidinium Bromide Post-Authorisation Safety Study to Evaluate the Risk of Cardiovascular Endpoints

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: Aclidinium bromide; Drug: Other COPD medication

• Registration Number: NCT03290287
• Lead Sponsor: AstraZeneca

Brief Summary

The purpose of this study is to evaluate the potential cardiovascular safety concerns and all-cause mortality described in the risk management plan for aclidinium bromide, through sequential, nested case-control studies for each endpoint of interest

Detailed Description

This is a post-authorisation safety study (PASS) of new users of aclidinium bromide, fixed dose aclidinium bromide/formoterol fumarate dihydrate, and other inhaled medications frequently used by patients with COPD

The plan is for the PASS study to be conducted on one population-based automated health database; the initial candidate database is the CRPD in the United Kingdom.

Study Timeline

• Study Start: 2017-03-01
• Study First Submitted: 2017-08-18
• Study First Submitted QC: 2017-09-19
• Study First Posted: 2017-09-21
• Primary Completion: 2022-06-30
• Study Completion: 2022-06-30
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-30
• Last Update Posted: 2023-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26839

Inclusion Criteria

1. Have at least 1 year of enrolment in the electronic database. In the CPRD, only patients with permanent registration status in "up to standard" participant general practices will be included in the cohort.
2. Be aged 40 years or older.
3. Have a recorded diagnosis of COPD.
4. Have not been prescribed a study medication of interest during the 6 months before the date of the first prescription for that specific study medication.

Exclusion Criteria

1. Patients with cancer or other serious, non-cardiovascular, life-threatening conditions or indicators of severe comorbidity will be excluded from the study cohort.
2. Subjects who will be potentially excluded are those with the following conditions recorded in the database at any time before the date of cohort entry: cancer, HIV, respiratory failure, end-stage renal disease or dialysis, organ transplantation, drug or alcohol abuse, coma, congenital abnormalities of the heart or great arteries.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
New users of aclidinium bromide	Aclidinium bromide	This nested cohort will be composed of patients aged 40 years or older who have previously been diagnosed with COPD and who are new users of aclidinium bromide (monotherapy; concomitant with formoterol not in fixed-dose combination; and aclidinium/formoterol)
New users of other COPD medication	Other COPD medication	This nested cohort will include patients aged 40 years or older who have previously been diagnosed with COPD and who are new users of other COPD medication: tiotropium, other LAMAs, LABA, LABA/ICS and LAMA/LABA.

Primary Outcome Measures

Name	Time	Method
Incidence rate of mortality from all causes	From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [January 2017]).	Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.

Secondary Outcome Measures

Name	Time	Method
Incidence rate of hospitalisation for acute myocardial infarction (fatal or non-fatal)	From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2021]).	Including community (out-of-hospital) coronary heart disease deaths. Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
Incidence rate of acute stroke (fatal or non-fatal)	From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2020]).	Including community (out-of-hospital) cerebrovascular disease deaths. Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
Incidence rate of new episodes of any type of diagnosed cardiac arrhythmia	From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2022]).	Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.
Incidence rate of first-ever hospitalisation for heart failure	From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period (2-3 months following start of data collection [First semester 2017]).	Age- and sex-standardised incidence rate per 1,000 person-years (95% CI). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.

Trial Locations

Locations (1)

Clinical Practice Research Datalink; 🇬🇧 London, United Kingdom