Early argipressin for adults with norepinephrine‑refractory vasoplegic shock

Efficacy of Early Argipressin (Arginine Vasopressin) in the Management of Intensive Care Patients With Norepinephrine-refractory Vasoplegic Shock: a Multicentric Randomized, Double-blind Placebo-controlled Superiority Trial

This trial will test whether giving argipressin early helps adults in the ICU whose vasoplegic shock does not respond to high‑dose norepinephrine.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 390 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Hospitalier Universitaire Dijon (Academic / other)
• Locations: 1 site (Dijon)
• Trial ID: NCT07063680 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial enrolls adults with vasoplegic shock who remain hypotensive despite high‑dose norepinephrine and meet objective hemodynamic criteria. Eligible patients must have a cardiac index ≥ 2.3 L/min/m², lactate > 2 mmol/L, require a norepinephrine‑equivalent dose ≥ 0.25 µg/kg/min, and have met refractory shock criteria for less than 12 hours. Participants receive argipressin in addition to standard ICU care while clinical data on hemodynamics, organ function, vasopressor exposure, and outcomes are collected. The trial is led by CHU Dijon Bourgogne and focuses on early second‑line vasopressin use in catecholamine‑refractory vasoplegia.

Who should consider this trial

Good fit: Adults (≥18 years) in the ICU with vasoplegic shock from causes such as sepsis, post‑operative vasoplegia, hemorrhage, sterile inflammation, anaphylaxis, or liver failure who have cardiac index ≥ 2.3 L/min/m², lactate > 2 mmol/L, require ≥ 0.25 µg/kg/min norepinephrine‑equivalent, and have been in refractory shock for under 12 hours.

Not a fit: Patients who do not meet the cardiac index or vasopressor thresholds, those with low‑output or primarily cardiogenic shock rather than vasoplegia, those already beyond 12 hours of refractory shock, or with contraindications to vasopressin may not receive benefit from this approach.

Why it matters

Potential benefit: If successful, early argipressin could speed shock reversal, reduce exposure to high‑dose catecholamines, and protect organ function such as the kidneys.

How similar studies have performed: Previous randomized and observational studies of vasopressin in catecholamine‑refractory vasoplegia and septic shock have shown mixed results with some vasopressor‑sparing and renal benefits but no consistent mortality advantage, so larger Phase 3 data are needed.

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

Where this trial is running

Dijon

• CHU Dijon Bourgogne — Dijon, France (Recruiting)

Study contacts

• Study coordinator: Maxime NGUYEN

Conditions Patients With Norepinephrine-refractory Vasoplegic Shock