Lead Investigator: Itsuki Osawa, Columbia University Irving Medical Center
Title of Proposal Research: Optimized timing of empagliflozin use for cardiorenal protection: a post-hoc analysis of the EMPA-REG OUTCOME, EMPEROR-REDUCED, and EMPEROR-PRESERVED clinical trials
Vivli Data Request: 10121
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Heart failure (HF) remains a significant cause of morbidity (illness) and mortality (death) worldwide, affecting approximately 6.2 million adults in the United States alone. In fact, heart failure was listed on 379,800 death certificates in 2018, accounting for 13.4 % of all recorded deaths. Empagliflozin is a medicine used to treat diabetes – a condition in which blood sugar levels are too high. It works by reducing the amount of glucose (sugar) that is returned to the blood by the kidneys, known as renal glucose reabsorption. The EMPA-REG OUTCOME clinical trial demonstrated the ability of empagliflozin to reduce rates of cardiovascular death and HF as well as to treat diabetes.
In several subsequent studies, empagliflozin has been shown to have beneficial effects in patients with HF. In patients with HF, both the EMPEROR-REDUCED and EMPEROR-PRESERVED studies showed that empagliflozin significantly reduced the risk of cardiovascular death, HF and major renal (kidney) events. The EMPA KIDNEY study also showed that empagliflozin was able to reduce the risk of progression of kidney disease or cardiovascular death compared to placebo (a treatment with no active ingredients). Although these studies confirm the therapeutic efficacy and safety of empagliflozin, there is still a lack of knowledge regarding the optimal timing of empagliflozin use for cardiorenal protection (e.g., earlier is better or timing does not affect treatment efficacy).
In this context, our proposed study aims to determine the optimal timing of empagliflozin initiation using machine learning (ML)-based algorithms. ML approaches have the potential to overcome the limitations of traditional analysis (e.g., pre-specified subgroup analysis) and hypothetically identify the optimal timing of empagliflozin use (e.g., from early to late disease stages). Our hypothesis is that the earlier empagliflozin is initiated, the greater the long-term effect on cardiorenal protection. This information may be useful to guide clinicians in prescribing empagliflozin at the right time to maximize its potential.
Requested Studies:
A Phase III, Multicentre, International, Randomised, Parallel Group, Double Blind Cardiovascular Safety Study of BI 10773 (10 mg and 25 mg Administered Orally Once Daily) Compared to Usual Care in Type 2 Diabetes Mellitus Patients With Increased Cardiovascular Risk
Data Contributor: Boehringer Ingelheim
Study ID: NCT01131676
Sponsor ID: 1245.25
A Phase III Randomised, Double-blind Trial to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg Compared to Placebo, in Patients With Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)
Data Contributor: Boehringer Ingelheim
Study ID: NCT03057951
Sponsor ID: 1245.110
A Phase III Randomised, Double-blind Trial to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg Compared to Placebo, in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
Data Contributor: Boehringer Ingelheim
Study ID: NCT03057977
Sponsor ID: 1245.121