Systematic Adjunction of Vasopressine in Septic Shock

NCT ID: NCT07052084

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2028-02-29

Brief Summary

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.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Vassopressine

Group Type: EXPERIMENTAL

Vasopressin administration

Intervention Type: DRUG

Low dose of vasopressin (0.02ui /min), maximum 5 days

Placebo

Group Type: PLACEBO_COMPARATOR

Sodium chloride administration

Intervention Type: DRUG

NaCl 0.9 %, maximum 5 days

Interventions

Vasopressin administration

Low dose of vasopressin (0.02ui /min), maximum 5 days

Intervention Type: DRUG

Sodium chloride administration

NaCl 0.9 %, maximum 5 days

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique Hopitaux De Marseille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

François Crémieux

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Marseille

Locations

Assistance Publique - Hôpitaux de Marseille

Marseille, , France

Countries

France

Central Contacts

Gary Duclos, MD

Role: CONTACT

gary.duclos@ap-hm.fr

04 91 96 55 31 ext. +33

Facility Contacts

Gary Duclos, MD

Role: primary

gary.duclos@ap-hm.fr

04 91 96 55 31 ext. +33

Other Identifiers

2024-513401-31-00

Identifier Type: CTIS

Identifier Source: secondary_id

RCAPHM23_0465

Identifier Type: -

Identifier Source: org_study_id