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

NCT07488689 | Not Yet Recruiting Phase 3

• 2 other identifiers: RC25_00522025-524820-23-00
• Study Type: interventional
• Target: 568
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Septic Shock

Keywords

microcirculatory dysfunction; septic shock; dapagliflozin; SGLT-2i; gliflozins

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

administration of once-daily oral dapagliflozin 10 mg for 7 days

Drug: Dapaglifozin

Placebo

PLACEBO COMPARATOR

administration of once-daily oral placebo for 7 days

Drug: Placebo

Interventions

Dapaglifozin DRUG

Oral Dapaglifozin 10mg once-daily administration, for 7 days

Dapagliflozin

Placebo DRUG

Oral Placebo once-daily administration, for 7 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient aged ≥ 18 years
• Hospitalized in ICU for septic shock according to Sepsis-3 definition (PMID: 26903338). Septic shock should be the primary reason for admission.
• Septic shock diagnosed for less than 12 hours prior to randomization
• Skin mottling (mottling score ≥ 2) according to Ait-Oufella and/or prolonged capillary refill time \> 3 seconds
• Patient benefiting from social health insurance (or having a close relative who is a beneficiary)
• 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

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Hôpital Civil, Service de médecine intensive et réanimation, Hôpitaux Universitaires de Strasbourg

Strasbourg, France

Location

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Ferhat MEZIANI, MD, PhD

  Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah HUSTACHE

CONTACT

03 88 11 54 15; dpidrci@chru-strasbourg.fr

Hamid MERDJI, MD, PhD

CONTACT

hamid.merdji@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2026
• First Posted: March 23, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): July 1, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

FR (1)