Post-Authorisation Safety Study of Lesinurad (SATURATES)

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.

Study Overview

• Status: Withdrawn
• Conditions: Hyperuricemia; Gout
• Intervention / Treatment: Drug: Zurampic®; Drug: Control group: xanthine oxidase inhibitor monotherapy

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients in this study will be 18 years of age or older, will have had at least 6 months (183 days) of continuous baseline data available before entering one of the cohorts, and will be current users of XOI monotherapy (i.e., > 1 dispensing/prescription of a study XOI in the 183-day baseline period prior to the index date and days' supply extending beyond the index date). The study population will include patients from one primary care database in Italy (Health Search) and another in Spain (Information System for Research in Primary Care [SIDIAP]), as well as two US health systems (the HealthCore Integrated Research DatabaseSM [HIRD] and Medicare).

Description

Inclusion Criteria:

• More than one dispensing/prescription for an xanthine oxidase inhibotor (XOI) within the past 183 days prior to the index date and days' supply extending beyond the index date
• A coded diagnosis of gout at any time in the past or on the index date
• Age 18 years or older
• Continuous enrolment in the database for the past 183 days

Exclusion Criteria:

• Patients on urate-lowering therapy medications within 6 months prior to the index date to manage gout (probenecid, benzbromarone, or pegloticase) other than an XOI (allopurinol, febuxostat) or lesinurad (not including medications to treat gout flares).
• Patients with severe renal impairment defined using clinical diagnostic codes (i.e., a diagnosis code of CKD stage IV, end-stage renal disease, or an indicator that eCrCl is < 30 mL/min at any time prior to the index date).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Zurampic®; Patients exposed to Zurampic® plus a xanthine oxidase inhibitor (allopurinol or febuxostat) (lesinurad+XOI)	Drug: Zurampic®; non-interventional study where patients are exposed to Zurampic® plus a xanthine oxidase inhibitor (allopurinol or febuxostat) during the normal course of clinical practice; Other Names: ATC code: M04A B05; Product name*: Zurampic®; Substance (INN)*: lesinurad
Control group: xanthine oxidase inhibitor monotherapy; Patients exposed to xanthine oxidase inhibitor monotherapy (allopurinol or febuxostat).	Drug: Control group: xanthine oxidase inhibitor monotherapy; non-interventional study where patients are exposed to xanthine oxidase inhibitor monotherapy (allopurinol or febuxostat) during the normal course of clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiac Events (MACE+)	MACE+ is 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.	2 year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalisation for acute kidney injury (AKI) including renal failure (with AKI as the primary diagnosis)	Confirmed cases of AKI require all three of the following criteria: A diagnosis of renal injury or acute renal injury recorded as a primary hospital discharge diagnosis in the electronic database AND; An increase in serum creatinine at hospital admission or within 48 hours of hospital admission defined as follows:Increase in serum creatinine by ≥ 1.5-fold from baseline where baseline is lowest value recorded within 1 year before the hospital admission date ORDecrease in estimated glomerular filtration rate (eGFR) or actual 24-hour GFR by ≥ 50% from baseline where baseline is highest value recorded within 1 year before the hospital admission date OREstimated creatinine clearance (eCrCl) < 30 mL/min AND; Absence of all the following contraindications for lesinurad patients at any time prior to the index date:A diagnosis code of chronic kidney disease stage IV or greatereCrCl < 30 mL/min recorded at any time prior to the index date	2 year follow-up
Each individual component of MACE+	This can be the hospitalisation for non-fatal AMI, stroke, or unstable angina and cardiovascular (CV) death.	2 year follow-up

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Anticipated): January 29, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: August 12, 2019
• First Submitted That Met QC Criteria: August 27, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 15, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia; Antirheumatic Agents; Gout Suppressants; Renal Agents; Uricosuric Agents; Lesinurad
• Other Study ID Numbers: D5310R00016; EUPAS30385 (Registry Identifier: EU PASS Register)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No