Status: Planned
First registered on:
08/08/2020
Last updated on:
08/08/2020
1. Study identification
EU PAS Register NumberEUPAS36689
Official titleComparative safety study of tramadol and codeine users: a population-based cohort study
Study title acronym
Study typeObservational study
Brief description of the studyDespite the growing awareness of the harms produced by chronic opioid use, tramadol is still favourably recommended by remarkable clinical guidelines , therefore we aimed to assess the incidence of adverse events among incident users of tramadol compared to codeine users among subjects ≥ 18 years old in Catalonia, Spain. We conducted a population-based cohort study using the SIDIAP database (www.sidiap.org) which is a primary care database that covers over 5 million subjects in Catalonia (Spain). We included all incident users of study drugs (tramadol/codeine) (2007-2017) with no use in the previous year and ≥18 years old, ≥1 year of valid data. We excluded those with
combined dispensation of tramadol and codeine in the same day as well as subjects with any of the outcome events of interest at the index date. Follow-up: (latest of) start of the study period or 1-year of valid data until (earliest of) end of enrolment, date of last capturing data, event of interest or end of follow-up. Our exposure were incident tramadol or codeine use (active comparator) and our outcomes, a composite cardiovascular event (cardiac arrythmia, heart failure, myocardial infarction, stroke), delirium, fractures, falls, sleep disorders, constipation, opioid dependence/abuse, all-cause mortality. Confounders: sociodemographic and socioeconomic characteristics, life style factors (alcohol and tobacco status), medical conditions and drugs, ATCs prescribed, GP visits, hospital admissions and traffic accidents. We calculated the
Incidence rates, absolute rate difference, and adjusted hazard ratios with 95% confidence intervals using cause-specific Cox proportional hazards regression model accounting for competing risk of death. Propensity-score matching was used to minimize confounding.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsIDIAPJGol
Department/Research groupInstitut Universitari d'Investigació en Atenció Primària Jordi Gol
Organisation/affiliationIDIAPJGol
Details of (Primary) lead investigator
Title Dr
Last name Carlen
First name Reyes
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
Spain
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed28/06/2018
Start date of data collection01/09/2020
Start date of data analysis
Date of interim report, if expected
Date of final study report30/09/2021
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government body
Research councils
EU funding scheme
OtherIDIAP Jordi Gol100
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Carlen
First name Reyes
Address line 1Gran Via Corts Catalanes, 587
Address line 2àtic
Address line 3
CityBarcelona
Postcode08007
CountrySpain
Phone number (incl. country code)0034934824110
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Carlen
First name Reyes
Address line 1Gran Via Corts Catalanes, 587
Address line 2àtic
Address line 3
CityBarcelona
Postcode08007
CountrySpain
Phone number (incl. country code)0034934824110
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)R05DA04
Substance class (ATC Code)N02AA79
Substance class (ATC Code)N02AJ06
Substance class (ATC Code)N02AJ07
Substance class (ATC Code)N02AJ08
Substance class (ATC Code)N02AJ09
Substance class (ATC Code)N02AJ13
Substance class (ATC Code)N02AJ14
Substance class (ATC Code)N02AJ15
Substance class (ATC Code)N02AX02
7. Medical conditions to be studied
Medical condition(s)Yes
Delirium
Drug abuse
Fear of falling
Drug dependence
Death
Cardiovascular disorder
Cerebrovascular accident
Constipation
Sleep disorder
Multiple fractures
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
9. Number of subjects
Estimated total number of subjects1186887
Additional information
In a previous feasibility study carried out to explore the expected population to be included, out of 7,251,277 subjects with data available in the SIDIAP database, 1,186,887 subjects were aged at least 18 years old and were prescribed an opioid painkiller during the period of study (2007-2016).
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Disease/case registry
Prescription event monitoring
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?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
To assess the incidence of adverse events among incident users of tramadol compared to codeine users among subjects ≥ 18 years old in Catalonia, Spain.
Are there primary outcomes?No
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
2007-2017 but further follow-up will be conducted with more data is available
15. Data analysis plan
Please provide a brief summary of the analysis method
Incidence rates (IR), absolute rate difference (RDs), and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using cause-specific Cox proportional hazards regression model accounting for competing risk of death. Propensity-score (PS) matching was used to minimize confounding.
Missing information:
Since the underlying data represent attended medical care, we assume that absence of information of clinical events means absence of that condition. Variables with missingness will treated as categorical with a missing category.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
