Status: Finalised
First registered on:
15/05/2014
Last updated on:
26/01/2021
1. Study identification
EU PAS Register NumberEUPAS6559
Official titleAclidinium Bromide Drug Utilisation Post-Authorisation Safety Studies (DUS): Common Protocol for Aclidinium (DUS1) and Aclidinium/Formoterol Fixed-Dose Combination (DUS2)
Study title acronym
Study typeObservational study
Brief description of the studyAclidinium bromide is a long-acting antagonist of lung M3 receptors used as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. For a post-authorization safety study, a multinational database drug utilisation study (DUS1) in a cohort of new users of aclidinium bromide and new users of other inhaled medications frequently used by patients with COPD will be implemented. DUS2 will begin when the fixed-dose combination of aclidinium bromide/formoterol fumarate becomes available. DUS1/DUS2 objectives are:
• To describe the characteristics and patterns of use of new users of aclidinium bromide (monotherapy or in combination with formoterol) and new users of other COPD medications.
• To evaluate the potential off-label use of aclidinium bromide
• To describe users of aclidinium bromide in subgroups of patients for whom there is missing information in the RMP
• To establish a core cohort of new users of aclidinium bromide for the future evaluation of safety concerns described in the RMP
The study is planned in the Clinical Practice Research Datalink, the German Pharmacoepidemiological Database, and the national health databases in Denmark. DUS1/DUS2 are non-interventional cohort studies of new users of aclidinium bromide (monotherapy or in combination, respectively), tiotropium, LABA, and LABA+ICS who will be characterised 1) at the index date according to prior clinical information and prior and concurrent use of medications and 2) during the year following the index date to assess patterns of use. All available new users of aclidinium bromide or of the fixed-dose combination of aclidinium/formoterol at study initiation in each database will be included. The estimated study target is 1,500-2,000 new users of aclidinium bromide (for DUS1;the fixed-dose combination of aclidinium/formoterol for DUS2) and a sample of 2,000 new users of each comparator in each country-specific database.
Was this study requested by a regulator?Yes: EMA
Is the study required by a Risk Management Plan (RMP)?
EU RMP category 3 (required)
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicableD6560R00005 (DUS1 - Eklira), and D6570R00002 (DUS2- Duaklir)
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsRTI-HS
Department/Research groupPharmacoepidemiology & Risk Management
Organisation/affiliationRTI Health Solutions
Details of (Primary) lead investigator
Title Dr
Last name Rebordosa
First name Cristina
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Multiple centres
In total how many centres are involved in this Study?3
Countries in which this study is being conducted
International study
Denmark
Germany
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed02/12/201310/01/2014
Start date of data collection30/06/201506/07/2015
Start date of data analysis14/07/201526/08/2015
Date of interim report, if expected31/03/201718/05/2017
Date of final study report29/05/202012/03/2020
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesAlmirall, S.A./AstraZeneca AB100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Rebordosa
First name Cristina
Address line 1Av. Diagonal 605, 9-1
Address line 2
Address line 3
CityBarcelona
Postcode08028
CountrySpain
Phone number (incl. country code)34933622807
Alternative phone number
Fax number (incl. country code)34934142610
Public Enquiries
Title Dr
Last name Rebordosa
First name Cristina
Address line 1Av. Diagonal 605, 9-1
Address line 2
Address line 3
CityBarcelona
Postcode08028
CountrySpain
Phone number (incl. country code)34933622807
Alternative phone number
Fax number (incl. country code)34934142610
6. Study drug(s) information
Substance class (ATC Code)Aclidinium bromide (R03BB05)
Substance class (ATC Code)Tiotropium bromide (R03BB04)
Substance class (ATC Code)Glycopyrronium bromide (R03BB06)
Substance class (ATC Code)Long-acting beta-agonists (LABA): formoterol (R03AC13), salmeterol (R03AC12), indacaterol (R03AC18)
Substance class (ATC Code)Fixed-dose combinations of LABA and inhaled corticosteroids: formoterol/budesonide (R03AK07), salmeterol/fluticasone (R03AK06)
Substance class (ATC Code)Aclidinium/formoterol (R03AL05)
7. Medical conditions to be studied
Medical condition(s)Yes
Chronic obstructive pulmonary disease
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
Other population
Renal impaired
Hepatic impaired
9. Number of subjects
Estimated total number of subjects22500
Additional information
Between 1,500 and 2,000 users of aclidinium and 2,000 users of each of the comparators (tiotropium, LABAs, and LABA+ICS) in each planned database (n=3).
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources not registered with ENCePP
National Health Databases, Denmark
Sources of data
Administrative database, e.g. claims database
Routine primary care electronic patient registry
Pharmacy dispensing records
11. Scope of the study
What is the scope of the study?
Drug utilisation study
Primary scope : Drug utilisation study
12. Main objective(s)
What is the main objective of the study?
Describe characteristics and patterns of use of new users of aclidinium bromide and other selected COPD treatments;
Evaluate potential off-label use of aclidinium bromide;
Describe users of aclidinium bromide in subgroups of patients for whom there is missing information in RMP;
Establish a core cohort of new users of aclidinium bromide for future evaluation of safety concerns described in RMP
Are there primary outcomes?No
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
Drug utilisation study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
To evaluate the patterns of use of the medications of interest, each member of the study cohorts will be followed from the first date the patient is prescribed aclidinium bromide or another selected COPD medication to the earliest of the following dates:
(1) 1 year from index date, or
(2) Death, or
(3) Disenrollment from the database.
15. Data analysis plan
Please provide a brief summary of the analysis method
The analysis will be descriptive and implemented in two phases:
Phase 1. Baseline analysis:
• Age and sex distribution of users
• Proportion of patients with the above listed characteristics, comorbidities, and comedications for up to 1 year before the index date.
• Proportion and description of patients with off-label use.
Phase 2. Follow-up analysis:
• Assessment of relevant comorbidities, pregnancies, and treatment patterns (duration, dose, and switching patterns) during 1 year after the index date.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
Rivero-Ferrer E, Witzleb AJ, Olesen M, Plana E, Aguado J, Saigi-Morgui N, Rubino A, Daoud SZ, Lei A, Perez-Gutthann S, Schink T, Kristiansen NS, Pottegard A, Rebordosa C. Are aclidinium and aclidinium/formoterol used according to their approved indication in Europe? Results of a multicountry drug utilization postauthorization safety study. Poster presented at the 36th International Conference on Pharmacoepidemiology & Therapeutic Risk Management, Virtual, September 16–17, 2020. [abstract] Pharmacoepidemiol Drug Saf. 2020 Oct; 29(Suppl 3):175.https://www.rtihs.org/publications/are-aclidinium-and-aclidiniumformoterol-used-according-their-approved-indication-europe
Plana E, Rebordosa C, Aguado J, Thomas S, Garcia-Gil E, Perez-Gutthann S, Castellsague J. Assessment of COPD severity in the UK CPRD. Poster presented at the 33rd ICPE International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 30, 2017. Montreal, Canada. [abstract] Pharmacoepidemiol Drug Saf. 2017 Aug; 26(Suppl 2):576https://www.rtihs.org/publications/assessment-copd-severity-uk-cprd
Rebordosa C, Rubino A, Witzleb AJ, Olesen M, Plana E, Aguado J, Saigi N, Daoud SZ, Lei A, Perez-Gutthann S, Schink T, Kristiansen NS, Pottegard A, Rivero-Ferrer E. Characteristics of new users of aclidinium, aclidinium/formoterol, and other COPD medications in three European countries. Poster presented at the 2020 Virtual ERS International Congress; October 2020. [abstract] Eur Respir J. 2020 Oct 28; 56(Suppl 64):2071. doi: 10.1183/13993003.congress-2020.2072.https://www.rtihs.org/publications/characteristics-new-users-aclidinium-aclidiniumformoterol-and-other-copd-medications
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documents
DescriptionDocumentLatest version
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
