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

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

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

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Aclidinium bromide; Drug: Other COPD medication

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 Type: Observational
• Enrollment (Anticipated): 31881

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Clinical Practice Research Datalink
    • Contact: Cristina Varas-Lorenzo, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study will be conducted in patients aged 40 years or older diagnosed with COPD initiating treatment with aclidinium bromide or other inhaled COPD treatments. Patients must have at least 1 year of enrolment in the electronic database and to have not been prescribed the study medication of interest during the 6-months before the date of the first prescription for that specific study medication. Patients with life-threatening non-cardiovascular comorbidity (e.g., malignancy, HIV infection, other) will be excluded

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
New users of 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)	Drug: Aclidinium bromide; Administered as monotherapy, concomitant with formoterol not in fixed-dose combination, or fixed-dose aclidinium/formoterol
New users of 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.	Drug: Other COPD medication; Users of the following COPD medications: Tiotropium Other long-acting anticholinergic (LAMAs): glycopyrronium bromide, umeclidinium LABA: formoterol, salmeterol, indacaterol LABA/ICS (LABA in fixed-dose combinations with ICS): formoterol/budesonide, formoterol/beclometasone, formoterol/mometasone, formoterol/fluticasone, salmeterol/fluticasone, and vilanterol/fluticasone. LAMA/LABA (approved or under regulatory review or in development): glycopyrrolate/formoterol, glycopyrronium/indacaterol, tiotropium/olodaterol, umeclidinium/vilanterol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of mortality from all causes	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.	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]).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of first-ever hospitalisation for heart failure	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.	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]).
Incidence rate of hospitalisation for acute myocardial infarction (fatal or non-fatal)	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.	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]).
Incidence rate of acute stroke (fatal or non-fatal)	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.	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]).
Incidence rate of new episodes of any type of diagnosed cardiac arrhythmia	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.	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]).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative risk of acute myocardial infarction, stroke, and out-of-hospital coronary heart disease or cerebrovascular death	A composite endpoint of acute myocardial infarction, stroke, and out-of-hospital coronary heart disease or cerebrovascular death (if confirmed that the direction and magnitude of the risk is similar across the individual components). Potential cases will be identified by general practitioner diagnosis, hospital discharge codes and mortality data from national statistics.	From the launch of Aclidinium Bromide in the UK (October 2012) to the end of the study period of individual components (2-3 months following start of data collection).
Incidence rate of new episodes of atrial fibrillation or flutter	Including episodes of paroxysmal (intermittent) atrial fibrillation or a new episode (first ever) or atrial fibrillation in patients without atrial fibrillation or flutter. 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.	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]).
Incidence rate of new episodes of serious ventricular arrhythmias (SVA)	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.	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]).

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: RTI Health Solutions

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: August 18, 2017
• First Submitted That Met QC Criteria: September 19, 2017
• First Posted (Actual): September 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Anticonvulsants; Bromides
• Other Study ID Numbers: D6560R00004; EUPAS13616 (Registry Identifier: ENCePP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No