Efficacy of Early Argipressin in the Management of Intensive Care Patients With Norepinephrine-refractory Vasoplegic Shock

NCT ID: NCT07063680

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 390 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2028-09-30

Brief Summary

Acute circulatory failure (shock) is defined as insufficient oxygen transport to meet the oxygen requirements of organs and tissues. Vasoplegic shock is the most frequent cause of shock, defined by vasoplegia and a drop in arterial pressure with preserved cardiac output. The main aetiologies of vasoplegic shock are sepsis and post-operative vasoplegia. Symptomatic treatment of vasoplegic shock is based on vasopressors. The first-line vasopressor is norepinephrine. Refractory vasoplegic shock refers as high norepinephrine requirements. In patients with catecholamine-refractory vasoplegia, the use of vasopressin as a second-line treatment is proposed. The use of vasopressin could improve organ and tissue perfusion, improve renal function, accelerate shock reversal and reduce patients' exposure to catecholamines, and thus to their side effects.

Currently, there is a gap between evidence and guidelines/practice regarding vasopressin in patients with refractory vasoplegic shock:

1. There are no large randomized control trial focusing on vasopressin use in patients with refractory vasoplegic shock and data extrapolated from non-refractory shock have contradictory conclusions regarding the benefit of vasopressin in this population.

2. In patients with vasoplegic shock, expert often recommend vasopressin as second line vasopressor and, in the case of septic shock, current international guidelines clearly position vasopressin as second-line therapy in septic shock and advocate its initiation in patients with vasoplegia refractory to norepinephrine.

The strengh of those recommendation is weak due to moderate quality of evidence highlighting the need to conduct a large randomized control trial on this topic.

We hypothesize that the use of vasopressin in patients with refractory vasoplegic shock may improve 30-day survival, decrease renal replacement therapy and reduce duration of vasopressor administration. This is the first multicentred study aiming to confirm the superiority of vasopressin in combination with norepinephrine over norepinephrine alone in this population.

Conditions

Patients With Norepinephrine-refractory Vasoplegic Shock

Study Design

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

Study Groups

Interventional group

Group Type: EXPERIMENTAL

Argipressin

Intervention Type: DRUG

Argipressin 0.4 U.ml-1 (i.e. 40IU diluted in 100ml 0.9% NaCl bag)

Collection of clinical data

Intervention Type: OTHER

At inclusion, D0 to D7, ICU discharge, D30 and D90

Standard group

Group Type: ACTIVE_COMPARATOR

Chlorure de sodium

Intervention Type: DRUG

NaCl 0.9%

Collection of clinical data

Intervention Type: OTHER

At inclusion, D0 to D7, ICU discharge, D30 and D90

Interventions

Argipressin

Argipressin 0.4 U.ml-1 (i.e. 40IU diluted in 100ml 0.9% NaCl bag)

Intervention Type: DRUG

Chlorure de sodium

NaCl 0.9%

Intervention Type: DRUG

Collection of clinical data

At inclusion, D0 to D7, ICU discharge, D30 and D90

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients aged ≥ 18 years
• Vasoplegic shock defined as patient requiring vasopressor at the time of inclusion AND with a cardiac index ≥ 2.3/L/min/m² [32] (measured by echocardiography, Swan-Ganz, pulse contour analysis or thermodilution) and with hyperlactatemia > 2 mmol/l.
• Vasoplegia must be primarily caused by one of the following etiologies:

• Sepsis (documented or clinically suspected infection)
• Post-operative vasoplegia (following cardiac or non-cardiac surgery)
• Post hemorrhage
• Sterile systemic inflammation (e.g., pancreatitis, burns, trauma)
• Anaphylaxis
• Liver failure
• Other causes of vasoplegia
• Refractory shock: dose of vasopressor (express as norepinephrine base equivalent) ≥ 0.25 μg/kg/min in order to maintain perfusion pressure within patient-defined targets (defined by the physician in charge of the patient).
• Early intervention: Criteria for refractory AND vasoplegic shock reached for less than 12 hours.
• Informed consent obtained from the patient or, if unable to give consent, a surrogate. If the surrogate is not available, emergency consent can be considered.
• Covered by French national health insurance

Exclusion Criteria

• Patients that do not present the criteria for vasoplegic AND refractory shock at the time of inclusion anymore (resolved condition)
• Ongoing vasopressin treatment
• Ongoing inotrope treatment (except norepinephrine)
• Ongoing acute coronary syndrome, mesenteric ischemia
• Uncontrolled active bleeding
• Vasoplegia due to neurogenic shock
• Vasospastic disease (Raynaud's disease, systemic scleroderma…)
• Hyponatremia <120 mmol l-1
• Known hypersensitivity to Argipressin or to any of the excipients of REVERPLEG®.
• Patient already enrolled in an interventional trial
• Decision to limit life-sustaining treatments
• Person under legal protection
• Pregnant, parturient or breastfeeding women

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

Sponsors

Centre Hospitalier Universitaire Dijon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU Dijon Bourgogne

Dijon, , France

Countries

France

Central Contacts

Maxime NGUYEN

Role: CONTACT

maxime.nguyen-soenen@chu-dijon.fr

03 80 29 35 28 ext. +33

Facility Contacts

Maxime NGUYEN

Role: primary

nguyen-soenen@chu-dijon.fr

03 80 29 35 28 ext. +33

Other Identifiers

NGUYEN PHRCN 2023

Identifier Type: -

Identifier Source: org_study_id