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

NCT ID: NCT05207280

Last Updated: 2023-04-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

152 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-11

Study Completion Date

2024-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Septic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, parallel, multicenter, double-blind clinical trial with two treatment arms
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
double-blind clinical trial

Study Groups

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Noradrenaline plus Terlipressin

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)

Group Type EXPERIMENTAL

Noradrenaline plus Terlipressin

Intervention Type COMBINATION_PRODUCT

Comparison Norepinephrine plus placebo versus Terlipressin plus Norepinephrine for the Treatment of Septic Shock

Noradrenaline plus placebo

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

Group Type PLACEBO_COMPARATOR

Noradrenaline plus Terlipressin

Intervention Type COMBINATION_PRODUCT

Comparison Norepinephrine plus placebo versus Terlipressin plus Norepinephrine for the Treatment of Septic Shock

Interventions

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Noradrenaline plus Terlipressin

Comparison Norepinephrine plus placebo versus Terlipressin plus Norepinephrine for the Treatment of Septic Shock

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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Noradrenaline plus placebo

Eligibility Criteria

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Inclusion Criteria

1. Adult patients (18 years or older).
2. Patients with septic shock
3. Patients with a SOFA \> 4 points.

5\. 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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José Garnacho Montero

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Virgen Macarena

Locations

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Hospital Universitario Jerez de la Frontera

Jerez de la Frontera, Cádiz, Spain

Site Status RECRUITING

Hospital San Juan de Dios del Aljarafe

Bormujos, Sevilla, Spain

Site Status RECRUITING

Hospital Puerta del mar

Cadiz, , Spain

Site Status RECRUITING

Hospital Universitario Reina Sofía

Córdoba, , Spain

Site Status RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Site Status RECRUITING

Hospital Universitario Clínico San Cecilio

Granada, , Spain

Site Status RECRUITING

Complejo Hospitalario de Jaén

Jaén, , Spain

Site Status RECRUITING

Hospital Universitario Regional de Málaga

Málaga, , Spain

Site Status RECRUITING

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Clara Rosso Fernández

Role: CONTACT

955012144

Irene Borreguero Borreguero

Role: CONTACT

955007609

Facility Contacts

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Rafael Estella García

Role: primary

José Luis García Garmendia

Role: primary

Rafael Sierra Camerino

Role: primary

Carmen de la Fuente Martos

Role: primary

María del Mar Jiménez Quintana

Role: primary

Manuel Colmenero Ruiz

Role: primary

Ricardo Rivera Fernández

Role: primary

Manuel Herrera Gutiérrez

Role: primary

Clara Rosso Fernández

Role: primary

955012144

Irene Borreguero Borreguero

Role: backup

955007609

Rosario Amaya Villar

Role: primary

Other Identifiers

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CONTENTSS

Identifier Type: -

Identifier Source: org_study_id

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