Post-authorisation safety study in patients with type 2 diabetes mellitus to assess the risk of acute liver injury, acute kidney injury and chronic kidney disease, severe complications of urinary tract infection, genital infections, and diabetic ketoacidosis among patients treated with empagliflozin compared to patients treated with DPP-4 inhibitors (PASS renal, liver injury, infection, ketoacidosis)

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/50541
• EU PAS number:
  EUPAS13413
• Study ID:
  50541
• Official title and acronym:
  Post-authorisation safety study in patients with type 2 diabetes mellitus to assess the risk of acute liver injury, acute kidney injury and chronic kidney disease, severe complications of urinary tract infection, genital infections, and diabetic ketoacidosis among patients treated with empagliflozin compared to patients treated with DPP-4 inhibitors (PASS renal, liver injury, infection, ketoacidosis)
• DARWIN EU® study:
  No
• Study countries:
  Denmark

  United Kingdom

  United States
• Study description:
  Empagliflozin (Jardiance), a highly potent and selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2), was approved in Europe in May 2014 for the treatment of type 2 diabetes mellitus (T2DM) to improve glycaemic control in adults. As part of the risk management plan, Boehringer Ingelheim International GmbH (BI) has committed to conduct a post-authorisation safety study (PASS) to evaluate the liver and renal safety of empagliflozin. The study will also evaluate the risks of severe complications of urinary tract infections (UTIs), genital infections and diabetic ketoacidosis. To evaluate the association between empagliflozin use and mentioned outcomes routinely collected health information from the Clinical Practice Research Datalink (CPRD), in the United Kingdom. For the evaluation of the rarest outcomes, the Danish Population Registries in Denmark and the HealthCore Integrated Research Database (HIRD) in the United States. This PASS will be conducted through an observational cohort study among adult patients with T2DM and at least 12 months of continuous enrolment in the data source where new users of empagliflozin will be compared to new users of dipeptidyl peptidase-4 (DPP4) inhibitors. Estimations will be made on the crude and adjusted incidence rates and adjusted incidence rate ratios of the primary and secondary outcomes. The primary outcomes will be: acute liver injury (ALI) in patients without predisposing conditions, acute kidney injury, severe complications of urinary tract infection, genital infections, and diabetic ketoacidosis. The secondary outcomes will be: ALI in patients with or without predisposing conditions, chronic kidney disease, and severe genital infections.
• Study status:
  Finalised

Research institution and networks

Institutions

RTI Health Solutions (RTI-HS)

France

Spain

Sweden

United Kingdom

United Kingdom (Northern Ireland)

United States

Clinical Practice Research Datalink (CPRD)

United Kingdom

HealthCore United States, Aarhus University Denmark

Contact details

Cristina Rebordosa

Study contact

[e-mail]

Cristina Rebordosa

Primary lead investigator

Study timelines

Date when funding contract was signed

Planned: 31/12/2015

Actual: 09/03/2016

Data collection

Planned: 30/03/2016

Actual: 15/03/2016

Start date of data analysis

Planned: 31/01/2020

Actual: 13/05/2021

Date of interim report, if expected

Planned: 15/06/2016

Actual: 20/06/2016

Date of final study report

Planned: 30/12/2022

Actual: 23/11/2022

Sources of funding

Pharmaceutical company and other private sector 

More details on funding

Boehringer Ingelheim International GmbH

Study protocol

Initial protocol

1245-96-protocol_v7.0_Final_redacted

Updated protocol

1245-96-protocol_v8.0_Final_redacted

Regulatory

• Was the study required by a regulatory body?:
  Yes
• Is the study required by a Risk Management Plan (RMP)?:
  EU RMP category 3 (required)