Clinical trial NCT03363464: Comparative Effectiveness of Empagliflozin in the US
Official title: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) Study Program
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2017-12-06
Enrollment: 230000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: T2DM eligible patients in Medicare fee for service, plans A, B, D; United Healthcare (Optum Clinformatics Data Mart); MarketScan (Truven Healthcare Analytics)

Brief summary: Empagliflozin, a sodium glucose co-transporter 2 (SGLT-2) inhibitor, was launched as a treatment for type 2 diabetes mellitus (T2DM) in the U.S. in August 2014. In contrast with several previous cardiovascular outcomes trials, which failed to demonstrate an association with a higher or a lower risk of cardiovascular outcomes associated with members of other recently marketed antidiabetic classes, the EMPA-REG OUTCOME trial has shown that patients at high cardiovascular risk randomized to empagliflozin vs. placebo, were associated with a reduced risk of hospitalization for heart failure, cardiovascular mortality, and all-cause mortality.

However, these and other findings arising from an extensive clinical trial program aimed at evaluating the efficacy and safety profile for empagliflozin have yet to be demonstrated in a non-trial environment. This study aims to investigate the transferability of the effects demonstrated in dedicated randomized clinical studies to a broader population under real world conditions.


Eligibility criteria: Inclusion criteria:

* Patients \>= 18 years old for Marketscan and Optum, and \>=65 years old for Medicare only
* Patients initiating empagliflozin or a DPP-4 inhibitor within the study period. Initiation was defined as no use of SGLT-2 inhibitors (canagliflozin, dapagliflozin, ertugliflozin) or DPP-4 inhibitors in the previous 12 months.
* Restriction to patients with a diagnosis of T2DM (ICD-9 Dx code of 250.x0 or 250.x2; ICD-10 Dx code of E11.x) in the 12 months prior to drug initiation.

Exclusion criteria:

* Patients with missing or ambiguous age or sex information.
* All patients who have less than 12 months of continuous registration in the database prior to initiation of empagliflozin or a DPP-4 inhibitor will be excluded.
* Patients with type 1 diabetes mellitus (T1DM) defined as at least 1 inpatient or outpatient codes in the 12 months prior to drug initiation.
* Secondary diabetes, and gestational diabetes in the 12 months prior to drug initiation
* History of cancer in the 5 years prior to drug initiation
* End-stage renal disease (ESRD) in the 12 months prior to drug initiation
* HIV diagnosis or treatment in the 12 months prior to drug initiation
* Organ transplant in the 12 months prior to drug initiation
* Patients that were in nursing homes in the 12 months prior to drug initiation
* Patients with concomitant SGLT-2 inhibitor and DPP-4 inhibitor initiation will also be excluded.
* Patients initiating more than one DPP-4i on cohort entry date will additionally be excluded Additional exclusion criteria apply.

Primary outcomes:
measure: 3-point major adverse cardiovascular events (MACE)
timeFrame: 60 months
measure: Hospitalization for heart failure (specific, based on primary inpatient diagnosis code)
timeFrame: 60 months
measure: Hospitalization for heart failure (broad, based on any inpatient diagnosis code)
timeFrame: 60 months
measure: Modified MACE
timeFrame: 60 months
measure: Composite of MI or stroke hospital admission for heart failure
timeFrame: 60 months
measure: All-cause mortality
timeFrame: 60 months
Secondary outcomes:
measure: Coronary revascularization procedure
timeFrame: 60 months
measure: Hospitalization for unstable angina
timeFrame: 60 months
measure: Composite of MI, stroke, unstable angina hospitalization or coronary revascularization
timeFrame: 60 months
measure: End-stage renal disease (ESRD)
timeFrame: 60 months
measure: Bone fracture
timeFrame: 60 months
measure: Diabetic ketoacidosis (Inpatient, primary position)
timeFrame: 60 months
measure: Diabetic ketoacidosis (Inpatient, any position)
timeFrame: 60 months
measure: Severe hypoglycemia
timeFrame: 60 months
measure: Urinary tract cancers
timeFrame: 60 months
measure: Lower-limb amputation
timeFrame: 60 months
measure: Acute kidney injury (Inpatient, primary)
timeFrame: 60 months
measure: Acute kidney injury (Inpatient, any position)
timeFrame: 60 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Bringham Women Hospital
state: Massachusetts
Study officials:
References:
citation: Patorno E, Pawar A, Franklin JM, Najafzadeh M, Deruaz-Luyet A, Brodovicz KG, Sambevski S, Bessette LG, Santiago Ortiz AJ, Kulldorff M, Schneeweiss S. Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care. Circulation. 2019 Jun 18;139(25):2822-2830. doi: 10.1161/CIRCULATIONAHA.118.039177. Epub 2019 Apr 8.