Assessing the Efficacy of Dapagliflozin as a Vasculoprotective Treatment in Septic Shock Patients With Microcirculatory Dysfunction (GLIFLOSHOCK)

Microcirculatory dysfunction is a key driver of organ failure and mortality in septic shock, characterized by endothelial injury and impaired vasoregulation. Despite its strong prognostic value, it remains unaddressed by current therapies. SGLT-2 inhibitors (SGLT-2i) have shown promising vasculoprotective, anti-inflammatory, and glucose-lowering effects that may help restore endothelial function, reduce vascular leakage, and manage stress-induced hyperglycemia-factors central to septic shock pathophysiology. Preclinical and clinical observational studies suggest potential benefits, but clinical research in this specific context is lacking. This trial aims to evaluate the efficacy and safety of SGLT-2i in septic shock patients with clinical signs of microcirculatory failure, addressing a critical unmet medical need.

Septic shock management relies on rapid infection control, hemodynamic stabilization with fluids and vasopressors, and supportive care, with corticosteroids used in select cases. However, this standardized approach faces major limitations due to patient heterogeneity, treatment-related complications (e.g., fluid overload, vasopressor side effects), and rising antimicrobial resistance. Adjunctive therapies have largely failed to improve outcomes, reflecting the complex pathophysiology of septic shock. These challenges highlight a pressing need for novel, targeted interventions and a shift toward personalized treatment strategies.

The investigators hypothesize that early administration of SGLT-2 inhibitors within 14 hours of septic shock onset in patients showing signs of microcirculatory dysfunction will improve 28-day outcomes mainly by targeting endothelial and microvascular injury. Expected benefits include reduced mortality and organ dysfunction, faster recovery with lower resource use, a favorable safety profile, and potential for global implementation as a cost-effective adjunctive therapy.

This study will be a multicenter, prospective, randomized, and comparative double-blind trial. All patients admitted with septic shock in the ICU will be screened for trial eligibility criteria.

After verifying the eligibility criteria and obtaining patient or family consent, or after an emergency inclusion procedure, eligible patients will be randomized in a 1:1 ratio to receive either Dapagliflozin (10 mg once daily) or matching placebo in addition to standard-of-care.

Patients will be followed up for 1 year or until death, whichever occurs first.

Study Overview

• Status: Not yet recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Dapaglifozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 568
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sarah HUSTACHE; Phone Number: +33 03 88 11 54 15; Email: dpidrci@chru-strasbourg.fr
• Study Contact Backup: Name: Hamid MERDJI, MD, PhD; Email: hamid.merdji@chru-strasbourg.fr

Study Locations

• France
  • Strasbourg, France
    • Hôpital Civil, Service de médecine intensive et réanimation, Hôpitaux Universitaires de Strasbourg
    • Contact: Hamid MERDJI, MD, PhD; Phone Number: +33 03 69 55 11 23; Email: hamid.merdji@chru-strasbourg.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient aged ≥ 18 years
2. Hospitalized in ICU for septic shock according to Sepsis-3 definition (PMID: 26903338). Septic shock should be the primary reason for admission.
3. Septic shock diagnosed for less than 12 hours prior to randomization
4. Skin mottling (mottling score ≥ 2) according to Ait-Oufella and/or prolonged capillary refill time > 3 seconds
5. Patient benefiting from social health insurance (or having a close relative who is a beneficiary)
6. Patient or legal representative having signed an informed consent to participate in the study. In case immediate consent is not possible, an emergency procedure will be applied in accordance with current regulations

Exclusion Criteria:

1. Patient in whom oral administration is not possible at the initial stage (e.g., emergency digestive surgery, acute mesenteric ischemia, etc.).
2. Patient treated with SGLT2 inhibitor before ICU admission
3. Hypoglycemia < 0.5 g/L (2.75 mmol/L)
4. End-stage kidney disease undergoing maintenance dialysis
5. Medical history of type 1 diabetes (gliflozins are not authorized for treatment of this type of diabetes)
6. Medical history of diabetic ketoacidosis
7. Ongoing Fournier's gangrene
8. Current treatment with lithium
9. Cirrhose child C
10. Do not resuscitate order at inclusion in the study
11. Concomitant participation in another interventional therapeutic trial
12. Patient deprived of liberty or under legal protection (guardianship, conservatorship, or legal protection)
13. Pregnancy or breastfeeding
14. Contraindications to dapagliflozin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; administration of once-daily oral dapagliflozin 10 mg for 7 days	Drug: Dapaglifozin; Oral Dapaglifozin 10mg once-daily administration, for 7 days
Placebo Comparator: Placebo; administration of once-daily oral placebo for 7 days	Drug: Placebo; Oral Placebo once-daily administration, for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite endpoint including all-cause mortality, weaning of vasopressor, and initiation of renal replacement therapy.	These outcomes will be observed up to 28 days post-randomization, with events censored at the point of hospital discharge	weaning of vasopressor: day 5, all-cause mortality: day 28, initiation of renal replacement therapy: day 28.

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Investigators: Principal Investigator: Ferhat MEZIANI, MD, PhD, Hopitaux Universitaires de Strasbourg

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: septic shock; dapagliflozin; gliflozins; SGLT-2i; microcirculatory dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Shock, Septic
• Other Study ID Numbers: RC25_0052; 2025-524820-23-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No