Systematic Adjunction of Vasopressine in Septic Shock (SAVSepticShock)

Systematic Adjunction of Vasopressine in Hyperkinetic Septic Shock Patients - A Multicentric RCT

Septic shock is a syndrome associated with severe infection and a mortality rate of approximately 45%. In line with current recommendations, norepinephrine is the first-line vasopressor used in patients with septic shock. In a previous study, norepinephrine doses above 1 µg/kg/min were associated with mortality rates over 90%. In the same study, doses above 0.3 µg/kg/min were associated with a mortality rate of 40%. An increased mortality compared to the general 40% mortality of septic shock appears to be associated with norepinephrine doses as low as 0.3 µg/kg/min.

Vasopressin stimulates V1 receptors, primarily located on vascular smooth muscle cells. When V1a receptors are stimulated, they induce vasoconstriction by activating protein kinase C via a Gq protein and various second messengers.

Its use is validated in refractory shock states by international guidelines as a second-line vasopressor. This indication was further reinforced in the 2021 update of the septic shock management recommendations.

The VASST study, a randomized controlled trial, assessed the effects of vasopressin versus norepinephrine in septic shock. It found no overall difference in mortality between the two groups. However, in less severe cases where norepinephrine doses were below 14 µg/min before randomization, vasopressin was associated with significantly lower mortality, suggesting potential benefits from early introduction of a second vasopressor.

The VANISH trial failed to confirm this hypothesis, possibly due to broad inclusion criteria and unclear protocol regarding the combined use of both agents. Our hypothesis is that (1) vasopressin is beneficial when used synergistically with norepinephrine; (2) due to its negative effect on cardiac output (as shown in previous studies), vasopressin should only be administered to patients in the hyperdynamic phase of septic shock.

The hypothesis is that the systematic addition of vasopressin to norepinephrine therapy in a hyperdynamic septic shock subpopulation would improve patient outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Vasopressin administration; Drug: Sodium chloride administration

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gary Duclos, MD; Phone Number: +33 04 91 96 55 31; Email: gary.duclos@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13005
    • Assistance Publique - Hopitaux de Marseille
    • Principal Investigator: Gary Duclos, MD
    • Contact: Gary Duclos, MD; Phone Number: +33 04 91 96 55 31; Email: gary.duclos@ap-hm.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient aged 18 or over
• Patient who has consented to take part in the research or patient whose close relative has consented to take part in the research or, failing that, patient being included in an emergency situation
• Patient in septic shock with adapted cardiac output
• Patient in whom noradrenaline dosage has been greater than 0.3μg/kg/min for less than 12 hours
• Patients benefiting from or affiliated to social security

Exclusion Criteria:

• Patient with acute coronary syndrome
• Patient with known history of acute coronary syndrome
• Patient with suspected mesenteric ischemia
• Patient with hyponatremia < 130mmol/L,
• Known allergy to vasopressin or its excipients
• Minors
• Pregnant women
• Patients under legal guardianship or curatorship
• Patients under judicial protection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Sodium chloride administration; NaCl 0.9 %, maximum 5 days
Experimental: Vassopressine	Drug: Vasopressin administration; Low dose of vasopressin (0.02ui /min), maximum 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SOFA score comparison between the two groups	Sepsis-related Organ Failure Assessment, 0 to 24 points (higher scores indicate more severe organ dysfunction)	48 hours after administration of experimental drug (H48)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality comparison between the two groups		28 days after administration of experimental drug (D28)
Lactatemia decrease comparison between the two groups		Between administration of experimental drug (H0), 24 hours after (H24), and 48 hours after (H48)
Noradrenaline use comparison between the two groups	Maximum dose	5 days after administration of experimental drug (D5)
Renal function comparison between the two groups	Number of days alive without renal replacement therapy	28 days after administration of experimental drug (D28)
Respiratory function comparison between the two groups	Number of days alive without mechanical ventilation	28 days after administration of experimental drug (D28)
Occurrence of myocardial ischemia comparison between the two groups		28 days after administration of experimental drug (D28)
Occurrence of cardiogenic shock comparison between the two groups		28 days after administration of experimental drug (D28)
Occurrence of mesenteric ischemia comparison between the two groups		28 days after administration of experimental drug (D28)
Occurrence of digital ischemia comparison between the two groups		28 days after administration of experimental drug (D28)
Occurrence of atrial fibrillation comparison between the two groups		28 days after administration of experimental drug (D28)
Occurrence of a thromboembolic event comparison between the two groups		28 days after administration of experimental drug (D28)
SOFA score comparison between the two groups	Sepsis-related Organ Failure Assessment, 0 to 24 points (higher scores indicate more severe organ dysfunction)	120 hours after administration of experimental drug (H120)

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: François Crémieux, Assistance Publique - Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: June 26, 2025
• First Submitted That Met QC Criteria: June 26, 2025
• First Posted (Actual): July 4, 2025

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Vasopressine; Systematic adjunction
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Shock, Septic; Physiological Effects of Drugs; Hemostatics; Coagulants; Natriuretic Agents; Vasoconstrictor Agents; Antidiuretic Agents; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: RCAPHM23_0465; 2024-513401-31-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No