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

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ClinicalTrials.gov Identifier: NCT03290287
Recruitment Status : Recruiting
First Posted : September 21, 2017
Last Update Posted : May 15, 2019
Sponsor:
Collaborator:
RTI Health Solutions
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment
Pulmonary Disease, Chronic Obstructive 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.


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Study Type : Observational
Estimated Enrollment : 15400 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Aclidinium Bromide Post-Authorisation Safety Study to Evaluate the Risk of Cardiovascular Endpoints: Common Study Protocol
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine


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





Primary Outcome Measures :
  1. Incidence rate of mortality from all causes [ Time Frame: 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 :
  1. Incidence rate of first-ever hospitalisation for heart failure [ Time Frame: 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.

  2. Incidence rate of hospitalisation for acute myocardial infarction (fatal or non-fatal) [ Time Frame: 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.

  3. Incidence rate of acute stroke (fatal or non-fatal) [ Time Frame: 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.

  4. Incidence rate of new episodes of any type of diagnosed cardiac arrhythmia [ Time Frame: 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.


Other Outcome Measures:
  1. Relative risk of acute myocardial infarction, stroke, and out-of-hospital coronary heart disease or cerebrovascular death [ Time Frame: 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). ]
    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.

  2. Incidence rate of new episodes of atrial fibrillation or flutter [ Time Frame: 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]). ]
    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.

  3. Incidence rate of new episodes of serious ventricular arrhythmias (SVA) [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03290287


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United Kingdom
Clinical Practice Research Datalink Recruiting
London, United Kingdom
Contact: Cristina Varas-Lorenzo, MD, PhD         
Sponsors and Collaborators
AstraZeneca
RTI Health Solutions

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03290287     History of Changes
Other Study ID Numbers: D6560R00004
EUPAS13616 ( Registry Identifier: ENCePP )
First Posted: September 21, 2017    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by AstraZeneca:
COPD

Additional relevant MeSH terms:
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Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive
Formoterol Fumarate
Bromides
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants