Clinical Trial Comparing Noradrenaline (NA) Plus Placebo Versus Noradrenaline Plus Terlipressin (TP) in Septic Shock

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Status and phase: Enrolling; Phase 3

Conditions: Septic Shock

Treatments: Combination Product: Noradrenaline plus Terlipressin

Study type: Interventional

Funder types: Other

Identifiers

NCT05207280

CONTENTSS

Details and patient eligibility

About

Septic shock is a major health problem. In the clinical practice guidelines of the Surviving Sepsis Campaign is recommended to add vasopressin (VP) or epinephrine in case of not reaching the goal of mean arterial pressure (MAP) although with a low level of evidence.

This is a clinical trial with the purpose of comparing the efficacy and safety of norepinephrine (NE) plus placebo versus NE plus terlipressin (TP) in adult patients with septic shock and with a Sepsis related Organ Failure Assessment score (SOFA)> 4 points. The primary objective will be a combined end-point: reduction of organic dysfunction measured at 72 h by SOFA score and by the increase in ICU (Intensive care unit) -free days measured at 28 days.

Full description

Introduction: Septic shock is a major health problem. The clinical practice guidelines of the Surviving Sepsis Campaign establish the use of NE if after resuscitation with fluids a MAP> 65 mm Hg is not achieved. In these guidelines, it is recommended to add VP or epinephrine in case of not reaching the goal of MAP although with a low level of evidence.

TP is a synthetic analogue of VP with a long half-life. Preliminary studies on the use of TP associated with NE have not shown a decrease in mortality, although a reduction in organic dysfunction at 72 h, with discordant data regarding the rate of adverse events.

Material and Methods: Randomized, parallel, double-blind and multicenter clinical trial with the purpose of comparing the efficacy and safety of NE plus placebo versus NE plus TP in adult patients with septic shock and with a SOFA score> 4 points. The threshold dose of NE> 0.2 µg / kg / min is chosen to associate the second vasopressor (TP or placebo). The primary objective will be a combined end-point: reduction of organic dysfunction measured at 72 h by SOFA score and by the increase in ICU -free days measured at 28 days. The secondary objectives will be: mortality at 28 and 90 days, the need of renal replacement therapies, mechanical ventilation-free days, vasopressor-free days, and adverse reactions. Sample size of 152 patients (76 per arm), stratified by center and severity of illness. In addition, 6 single nucleotide polymorphisms of the vasopressin V1a receptor and a polymorphism of leucyl / cystinyl aminopeptidase or vasopressinase will be determined to establish its association with mortality in septic shock and with the efficacy and the occurrence of adverse effects due to the use of TP.

Enrollment: 152 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Adult patients (18 years or older).

2. Patients with septic shock

3. Patients with a SOFA > 4 points.

4. Oxygen saturation in the central venous system > 70% 5. Central venous pressure> 8 mmHg. 6. Signature of the informed consent by the patient or her legal representative.

Exclusion criteria

1. Pregnant or lactating patients.
2. Pathologies in which terlipressin is clinically indicated: gastrointestinal bleeding due to esophageal-gastric varices, hepatorenal syndrome.
3. Patients diagnosed with unstable acute coronary syndrome.
4. Patients with acute or chronic mesenteric ischemia.
5. Patients with Raynaud's Phenomenon, or vasospastic disease.
6. Patients participating in another intervention clinical trial.
7. Patients with active bleeding.
8. Patients with renal replacement technique at the time of randomization.
9. Patients with some limitation of life support treatment
10. Previous use of terlipressin during your stay in the intensive Care Unit

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

152 participants in 2 patient groups, including a placebo group

Noradrenaline plus Terlipressin

Experimental group

Description:

Patients enrolled in this arm, will receive noradrenaline with dose equal to or greater than 0.2 μg / Kg / min for at least 3 hours. Solution for infusion (Intravenous). And: Terlipressin with dose 1 mg every 6 hours diluted in a 50 mL serum to pass in 15-30 minutesin injectable solution. Intravenous (diluted in a 50 mL serum to pass in 15-30 minutes)

Treatment:

Combination Product: Noradrenaline plus Terlipressin

Noradrenaline plus placebo

Placebo Comparator group

Description:

Patients enrolled in this arm, will receive noradrenaline with dose equal to or greater than 0.2 μg / Kg / min for at least 3 hours in solution for infusion (Intravenous), and placebo with solution in vial with the same external appearance as terlipressin. 1 mg every 6 hours, diluted in a 50 mL serum to pass in 15-30 minutes in injectable solution Route of administration: Intravenous, diluted in a 50 mL serum to pass in 15-30 minutes

Treatment:

Combination Product: Noradrenaline plus Terlipressin