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 : Vaso²R

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Dijon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Trial duration

27 Mar 2026 → ongoing

Decision date (initial)

2025-06-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy (reduction of mortality, reduction of renal replacement therapy duration, reduction of vasopressor administration) of early Argipressin treatment (arginine vasopressin, REVERPLEG®) compared to placebo in adult patients with refractory vasoplegic shock

Secondary objectives 8

1. Efficacy objectives: To evaluate in comparison with placebo, whether Argipressin, is associated with: 1.A decrease in all-cause mortality in ICU, at day 30 (D30) and 90 (D90)
2. Efficacy objectives: To evaluate in comparison with placebo, whether Argipressin, is associated with: 2.A lower risk of renal failure at D30 and D90
3. Efficacy objectives: To evaluate in comparison with placebo, whether Argipressin, is associated with: 3.Lower incidence of cardiac complications within 7 days
4. Efficacy objectives: To evaluate in comparison with placebo, whether Argipressin, is associated with: 4.A lower overall dose of concomitant inotropic and vasopressor agents within 7 days
5. Efficacy objectives: To evaluate in comparison with placebo, whether Argipressin, is associated with: 5.Lower need for organ support at D30 and D90
6. Efficacy objectives: To evaluate in comparison with placebo, whether Argipressin, is associated with: 6.A shorter duration of hospitalisation in intensive care unit (ICU)
7. Efficacy objectives: To evaluate in comparison with placebo, whether Argipressin, is associated with: 7.A shorter duration of hospital stay
8. Safety objective: 8.To evaluate the safety of Argipressin in adult patients with refractory vasoplegia

Conditions and MedDRA coding

norepinephrine-refractory vasoplegic shock

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients aged ≥ 18 years
2. Vasoplegic shock: patient requiring vasopressor AND with a cardiac index ≥ 2.3/L/min/m² (measured by echocardiography, Swan-Ganz, pulse contour analysis or thermodilution) AND with hyperlactatemia > 2 mmol/l.
3. 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
4. Early intervention: Criteria for refractory AND vasoplegic shock reached for less than 12 hours.
5. 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.
6. Covered by French national health insurance
7. 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

Exclusion criteria 13

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite score including 3 criterions ordered from most to the least important: -mortality at D30 -use of renal replacement therapy (RRT) within 30 days post-inclusion -persistance of vasopressor use within 15 days post-inclusion. The score is calculated by comparing each patient from one group to all patients from the other group in the concerned strata (stratified win-ratio analysis).

Secondary endpoints 8

1. Efficacy objectives: comparison between experimental group and placebo group: 1.number of all cause deaths in ICU, at D30 and D90
2. Efficacy objectives: comparison between experimental group and placebo group: 2.renal failure (score ≥ 2 on the kidney disease improving global outcome (KDIGO) classification) at D30 and D90
3. Efficacy objectives: comparison between experimental group and placebo group: 3.Arrhythmia requiring treatment, myocardial injury within 7 days
4. Efficacy objectives: comparison between experimental group and placebo group: 4.Vasoactive Inotropic Score (VIS) between day 0 (D0) and 7 (D7)
5. Efficacy objectives: comparison between experimental group and placebo group: 5.Renal replacement therapy free days, vasopressor free days ventilator free days at D30 and D90
6. Efficacy objectives: comparison between experimental group and placebo group: 6.Length of stay (days) in intensive care unit (ICU)
7. Efficacy objectives: comparison between experimental group and placebo group: 7.Length of stay (days) until discharge from hospital
8. Safety objectives: 8.Number of serious adverse events according to the MedDRA classification in both groups

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Dijon

Sponsor organisation

Centre Hospitalier Universitaire De Dijon

Address

2 Boulevard Mal De Lattre De Tassigny

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

Chef de projets recherche

Public contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

Chef de projets recherche

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications