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

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/42316
• EU PAS number:
  EUPAS13616
• Study ID:
  42316
• Official title and acronym:
  Aclidinium Bromide Post-Authorisation Safety Study to Evaluate the Risk of Cardiovascular Endpoints
• DARWIN EU® study:
  No
• Study countries:
  United Kingdom
• Study description:
  Aclidinium bromide is a long-acting and potent antagonist of lung M3 receptors indicated as a maintenance bronchodilator treatment to relieve symptoms in adults age 40 or older with chronic obstructive pulmonary disease (COPD). To evaluate potential cardiovascular safety concerns and all-cause mortality identified in the European risk management plan for aclidinium bromide, a PASS will be conducted through sequential studies for the endpoints of interest. Specific aims are: ; --To compare the risk of congestive heart failure, acute myocardial infarction, stroke, and all-cause mortality in patients with COPD initiating treatment with aclidinium bromide (monotherapy or combination therapy with formoterol (not fixed-dose and fixed-dose) and other COPD medications with the risk in patients with COPD initiating treatment with long-acting beta-agonists (LABAs). ; --To compare the risk of the study endpoints of interest in patients with COPD initiating treatment with aclidinium bromide (monotherapy or combination with formoterol, not fixed-dose and fixed-dose) with the risk in patients with COPD initiating treatment with other COPD medications. ; --To evaluate the effect of dose and duration of each study medication on the risk of each study outcome. ; --To compare the risk of cardiac arrhythmias in patients with COPD between: ; 1) New users of fixed-dose combination of aclidinium and formoterol and other fixed-dose combination COPD medications with new users of LABA, ; 2) New users of fixed-dose combination of aclidinium and formoterol with new users of each of the other fixed-dose combination COPD medications. ; The first and second nested case-control and cohort studies, initiated in March 2016 and February 2017, evaluate the risk of all-cause mortality and congestive heart failure. Sample size considerations will trigger the start of three additional cohort studies evaluating the risk of acute myocardial infarction, stroke, and cardiac arrhythmias.
• Study status:
  Finalised

Research institutions and networks

Institutions

RTI Health Solutions (RTI-HS)

France

Spain

Sweden

United Kingdom

United Kingdom (Northern Ireland)

United States

Study timelines

Date when funding contract was signed

Planned: 29/02/2016

Actual: 10/03/2016

Study start date

Planned: 31/10/2016

Actual: 27/01/2017

Data analysis start date

Planned: 31/10/2017

Actual: 16/10/2017

Date of interim report, if expected

Planned: 28/06/2019

Actual: 06/06/2019

Date of final study report

Planned: 30/12/2023

Actual: 17/12/2023

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

AstraZeneca, Covis Pharma

Study protocol

Initial protocol

PASS_PROTOCOL_COMBO_2Jun2015_V 2.2_Redacted2

Updated protocol

D6560R00004 PASS protocol v4 signed_redacted

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  EU RMP category 1 (imposed as condition of marketing authorisation)