PubMed16 Apr 2026BMJ open● 6/10i Dapagliflozin for cardiorenal protection after intensive care unit discharge: a protocol for a randomised controlled trial evaluating dapagliflozin at ICU discharge for cardiorenal protection (DAPA-ICU).
Dépret F, Chousterman B, Roger C, Garnier M, Lalande R et al.
DAPA-ICU will test dapagliflozin versus placebo for one year in 600 adults at high cardiorenal risk following ICU discharge, targeting a composite of death, heart failure hospitalization, and renal decline. Multicentre, double-blind RCT across 16 French ICUs enrolling mechanically ventilated patients with elevated cardiac or renal biomarkers. This represents the first trial extending SGLT2 inhibitor cardiorenal protection to critically ill survivors, a population with 22% one-year mortality. Single-country study limits global generalizability.
Strategic Signal
DAPA-ICU could establish the first indication for SGLT2 inhibitors in post-critical care, potentially expanding dapagliflozin's addressable market beyond diabetes, heart failure, and chronic kidney disease. Success would provide AstraZeneca competitive differentiation in cardiorenal protection and create a new treatment paradigm for the estimated 5.7 million annual ICU survivors globally. The trial design targeting high-risk patients with elevated biomarkers mirrors successful SGLT2 strategies in heart failure and CKD, suggesting regulatory precedent exists for broad cardiorenal indications.
Original Abstract
INTRODUCTION: Patients discharged from intensive care units (ICUs) are at high risk of adverse long-term outcomes including cardiovascular and/or renal events and a 1-year mortality of approximately 22%. Plasma biomarkers measured at ICU discharge have demonstrated strong prognostic value, with elevated cardiac or renal biomarkers identifying patients at particularly high risk of poor outcomes. Sodium-glucose cotransporter 2 inhibitors are now widely recognised for their cardioprotective and nephroprotective effects in chronic conditions such as type 2 diabetes, heart failure or chronic kidney disease. These agents improve both morbidity and mortality across a range of high-risk populations. We hypothesise that a therapeutic strategy aimed at preventing the progression of cardiovascular and/or renal injury following ICU discharge may improve long-term outcomes in ICU survivors. METHOD AND ANALYSIS: This is a multicentre, double-blind, randomised, placebo-controlled clinical trial conducted across 16 teaching and non-teaching ICUs in France. We will enrol 600 adult patients (18 years of age or older) who have received mechanical ventilation and/or vasopressors for at least 24 hours during their ICU stay, and who meet at least one of the following criteria at ICU discharge: N-terminal pro-B-type natriuretic peptide (NT-proBNP) >800 pg/mL or BNP >90 ng/L, an estimated glomerular filtration rate between 25 and 90 mL/min/m². Eligible patients will be randomised in a 1:1 ratio to receive either dapagliflozin (10 mg once daily) or a matching placebo for a duration of 1 year. The primary outcome is a composite endpoint assessed at 1 year after randomisation, comprising: all-cause mortality, unscheduled hospitalisation for acute heart failure and decrease in renal function. Feasibility will be assessed based on patient and clinical acceptability and recruitment performance, including enrolment rates across participating centres. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board (CPP Ile-de-France 5). Written informed consent will be obtained from all participants prior to enrolment and the initiation of any study-related procedures. Dapagliflozin is a widely available medication with an established safety profile. If proven effective, it would represent a readily deployable strategy to improve long-term outcomes in ICU survivors. The study is described in accordance with the Standard Protocol Items: Recommendations for Interventional Trials framework, and key design features and methodological decisions are outlined accordingly. DAPA-ICU aims to evaluate the efficacy of dapagliflozin in cardiorenal protection among critically ill patients following ICU discharge. The main trial results will be submitted for publication in a peer-reviewed journal as soon as they become available after final analysis. TRIAL REGISTRATION NUMBER: NCT07025629.