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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

Chlorure de sodium: NaCl 0.9%

Collection of clinical data: At inclusion, D0 to D7, ICU discharge, D30 and D90

Study 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.

Eligibility

Primary outcome measure(s)

• The mortality rate — At Day 30
  in order to determine whether the administration of vasopressin in addition to norepinephrine improves survival
• The use of renal replacement therapy within 30 days post-inclusion — At Day 30
  in order to determine whether the administration of vasopressin in addition to norepinephrine improves renal function
• The persistence of vasopressor use within 15 days post-inclusion — At Day 15
  to determine whether the administration of vasopressin in addition to norepinephrine reduce the duration of shock

Trial sites (1)

More Centre Hospitalier Universitaire Dijon trials in France