Status: Planned
First registered on:
05/07/2019
Last updated on:
22/11/2021
1. Study identification
EU PAS Register NumberEUPAS30385
Official titleAn Observational Post-Authorisation Safety Study of Lesinurad Patients
Study title acronymSATURATES
Study typeObservational study
Brief description of the study*The study was withdrawn as Lesinurad was withdrawn from the market in Europe by the market authorization holder. Hence the commitment to do this PASS was removed by the European Medicines Agency.*
- Non-interventional population-based prospective cohort study in multiple databases comparing patients with gout who initiate lesinurad in combination with an existing xanthine oxidase inhibitor (XOI) (lesinurad+XOI cohort) to a propensity score-matched cohort of similar patients from the same data source who continue treatment with XOI monotherapy (XOI mono cohort). Study will characterize the cardiovascular safety of lesinurad in combination with XOI in patients with gout aged 18+ years compared with similar patients who continue XOI monotherapy. Primary objective: to assess the relative incidence of major adverse cardiac events plus hospitalization for unstable angina (MACE+ events) in patients with gout in both cohorts. Secondary objectives: to describe the characteristics of the cohorts prior to matching; to assess the relative incidence of hospitalisation for acute kidney injury between the matched cohorts; to assess the relative incidence of individual MACE+ components in the matched cohorts.
Was this study requested by a regulator?Yes: EMA
Is the study required by a Risk Management Plan (RMP)?
EU RMP category 1 (imposed as condition of marketing authorisation)
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicableD5310R00016
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsRTI-HS
Department/Research groupEpidemiology
Organisation/affiliationRTI Health Solutions
Details of (Primary) lead investigator
Title Dr
Last name Rivero
First name Elena
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?4
HealthCore, United States
Countries in which this study is being conducted
International study
Italy
Spain
United States
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed15/03/201630/03/2016
Start date of data collection30/09/2021
Start date of data analysis30/11/2021
Date of interim report, if expected
Date of final study report30/09/2024
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesAstra Zeneca100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Rivero
First name Elena
Address line 11800 Concord Pike
Address line 2PO Box 15437
Address line 3
CityWilmington, De
Postcode19850
CountryUnited States
Phone number (incl. country code)0018772409479
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name AstraZeneca
First name Clinical Study Information Center
Address line 11800 Concord Pike
Address line 2PO Box 15437
Address line 3
CityWilmington, De
Postcode
CountryUnited States
Phone number (incl. country code)0018772409479
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)M04AB (lesinurad)
Product NameZurampic
CountryUnited States
Substance INN(s)LESINURAD
7. Medical conditions to be studied
Medical condition(s)Yes
Hyperuricaemia
Gout
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 subjects131200
Additional information
Study size target is 16,400 person-years of follow-up in the matched cohorts for each data source (~3,300 person-years in the lesinurad+XOI cohort and ~13,100 person-years in the XOI mono cohort). To calculate estimated number of subjects, a 6-month duration was assumed; thus 16,400 person-years x 0.5 years = 32,800 persons as target in each data source. The target for lesinurad users is 6,600.
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Data sources not registered with ENCePP
HealthCore Integrated Research Database (HIRD), United States
Medicare, United States
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?
Risk assessment
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
To assess the relative incidence of major adverse cardiac events plus hospitalization for unstable angina (MACE+) events in patients with gout after lesinurad is added to their existing XOI therapy regimen and in patients continuing on XOI monotherapy.
Are there primary outcomes?Yes
Major Adverse Cardiac Events (MACE+), a composite endpoint comprised of: hospitalisation for non-fatal AMI, stroke, or unstable angina and cardiovascular (CV) death. CV death includes the following causes, occurring in or out of the hospital: AMI, sudden cardiac, heart failure, CV procedures, CV haemorrhage, stroke, underlying cerebrovascular cause, other CV causes.
Are there secondary outcomes?Yes
Hospitalisation for AKI including renal failure (with AKI as the primary diagnosis) and each individual component of MACE+.
13. Study design
What is the design of the study?
Non-interventional population based prospective cohort study
14. Follow-up of patients
Will patients be followed up?Not applicable/no follow-up
15. Data analysis plan
Please provide a brief summary of the analysis method
Characteristics for both cohorts will be summarised at the index date. The primary effect estimate is the relative incidence and 95% CI of MACE+ during person-time exposed to lesinurad+XOI compared to that exposed to XOI mono. Time to event for the primary analysis is the day after the start of the index treatment until the first occurrence of a MACE+ or censoring event. Descriptive analyses of MACE+ events and person-time of follow-up will be stratified by patient age group and history of CV disorders. Analysis for secondary endpoints will be conducted analogously.
Sensitivity analyses will evaluate the robustness of the estimate for the relative incidence of MACE+ between the two cohorts by differing assumptions for inclusion criteria, exposure definition, outcome definition, and potential unmeasured confounding.
If feasible, separate pooled analyses of European data sources and US data sources may be performed.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
Not submitted
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
Conflict(s) of interest of
investigator(s)Not submitted
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
