E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with septic shock who remain without reaching the hemodynamic goal of TAM> 65 mmHg, despite volume replacement and administration of noradrenaline at doses equal to or greater than 0.2 μg / Kg / min. |
Pacientes con shock séptico que permanecen sin alcanzar el objetivo hemodinámico de MBP > 65 mmHg, a pesar de la reposición de volumen y administración de noradrenalina a dosis igual o superior a 0,2 μg/Kg/min. |
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E.1.1.1 | Medical condition in easily understood language |
Serious illness caused by infection |
Enfermedad grave producida por un ainfección |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040070 |
E.1.2 | Term | Septic shock |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040089 |
E.1.2 | Term | Septicemia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Main objective is composed by: -Reduction of organ failure evaluated by Sepsis realted Organ failure Assessment score (SOFA scale) 72 h after administration of terlipressin / placebo. -Increase in ICU-free days of life measured 28 days after administration of terlipressin / placebo |
Será un objetivo combinado: -Reducción del fallo de órganos evaluado por escala SOFA (del inglés, Sepsis related Organ Failure Assessment) a las 72 h de la administración de terlipresina/placebo. -Incremento de los días con vida libres de UCI medidos a los 28 días de la administración de terlipresina/placebo |
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E.2.2 | Secondary objectives of the trial |
-Increase in lactate clearance at 6, 12, 24 and 72 h after administration of terlipressin / placebo -Increase in the days with life free of mechanical ventilation measured at 28 days -Increase in vasopressor-free days of life measured at 28 days -Mortality at 28 days and 90 days -Reduction of the need for continuous renal replacement therapy -Reduction of the total equivalent dose of vasopressors -No increase in adverse effects related to the administration of vasopressors. -Association with mortality of genetic variants of the vasopressin receptor 1a and LNPEP. -Association between achievement of the combined primary objective and genetic variants of the vasopressin receptor 1a and LNPEP. -Association between the appearance of adverse effects due to the use of terlipressin and genetic variants of the vasopressin receptor 1a and LNPEP. |
-Aumento en el aclaramiento de lactato a las 6, 12, 24 y 72 h de la administración de terlipresina/placebo -Incremento de los días con vida libres de ventilación mecánica medidos a los 28 días -Incremento de los días con vida libres de vasopresores medidos a los 28 días -Mortalidad a los 28 días y a los 90 días -Reducción de la necesidad de terapias continuas de reemplazo renal (TCRR) -Reducción de la dosis equivalente total de vasopresores -No incremento de efectos adversos relacionados con la administración de vasopresores. -Asociación con mortalidad de variantes genéticas del receptor de vasopresina 1a y LNPEP. -Asociación entre consecución de objetivo primario combinado y variantes genéticas del receptor de vasopresina 1a y LNPEP. -Asociación entre aparición de efectos adversos por uso de terlipresina y variantes genéticas del receptor de vasopresina 1a y LNPEP. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult patients (18 years or older). 2. Patients with septic shock. 3. Patients with a SOFA index> 4 points. 4. Venous oxygen saturation (SvO2)> 70% 5. Central venous pressure (CVP)> 8 mmHg. 6. Signature of the informed consent by the patient or his or her legal representative. |
1. Pacientes adultos (18 años o más). 2. Pacientes con shock séptico (ver definiciones). 3. Pacientes con un índice de SOFA > 4 puntos. 4. Saturación de oxígeno en el sistema venoso central (ScvO2) > 70 % 5. Presión Venosa Central (PVC) > 8 mmHg. 6. Firma del consentimiento informado por el paciente o su representante legal. |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating patients. 2. Pathologies on 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 (LLST). 10. Previous use of terlipressin during your stay in the ICU. |
1. Pacientes embarazadas o en período de lactancia. 2. Patologías en las que la terlipresina está clínicamente indicada: hemorragia digestiva por varices esófago-gástricas, síndrome hepatorenal. 3. Pacientes diagnosticados de síndrome coronario agudo inestable. 4. Pacientes con isquemia mesentérica aguda o crónica. 5. Pacientes con Fenómeno de Raynaud, o enfermedad vasospástica. 6. Pacientes participando en otro ensayo clínico de intervención. 7. Pacientes con hemorragia activa. 8. Pacientes que en el momento de la aleatorización se encuentren con técnica de reemplazo renal. 9. Pacientes con alguna limitación de tratamiento de soporte vital (LTSV). 10. Uso previo de terlipresina durante su estancia en UCI. |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Reduction of organ failure evaluated by SOFA scale -Increase in ICU-free days of life. |
-Reducción del fallo de órganos evaluado por escala SOFA. -Incremento de los días con vida libres de UCI. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Reduction of organ failure evaluated by SOFA scale 72 hours after administration of terlipressin / placebo. -Increase in ICU-free days of life measured 28 days after administration of terlipressin / placebo. |
-Reducción del fallo de órganos evaluado por escala SOFA a las 72 horas de la administración de terlipresina/placebo. -Incremento de los días con vida libres de UCI medidos a los 28 días de la administración de terlipresina/placebo. |
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E.5.2 | Secondary end point(s) |
-Increase in lactate clearance. -Increase of the days with life free of mechanical ventilation. -Increase in vasopressor-free days of lif. -Mortality. -Reduction of the need for continuous renal replacement therapy (CRRT). -Reduction of the total equivalent dose of vasopressors. -No increase in adverse effects related to the administration of vasopressors. -Association of mortality with genetic variants of the vasopressin 1a receptor and the LNPEP gene. -Association between the achievement of the combined primary endpoint and the genetic variants of the vasopressin receptor 1a and the LNPEP gene. -Association between the appearance of adverse effects due to the use of terlipressin, and the genetic variants of the Vasopressin 1a receptor and LNPEP gene. |
-Aumento en el aclaramiento de lactato. -Incremento de los días con vida libres de ventilación mecánica. -Incremento de los días con vida libres de vasopresores . -Mortalidad. -Reducción de la necesidad de terapias continuas de reemplazo renal (TCRR). -Reducción de la dosis equivalente total de vasopresores. -No incremento de efectos adversos relacionados con la administración de vasopresores. -Asociación con mortalidad de variantes genéticas del receptor de vasopresina 1a y el gen LNPEP. -Asociación entre consecución de objetivo primario combinado y variantes genéticas del receptor de vasopresina 1a y el gen LNPEP. -Asociación entre aparición de efectos adversos por uso de terlipresina y variantes genéticas del receptor de Vasopresina 1a y gen LNPEP. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Increase in lactate clearance at 6, 24 and 72 hours after administration of terlipressin / placebo. -Increase in the days of life free of mechanical ventilation measured at 28 days. -Increase in vasopressor-free days of life measured at 28 days. -Mortality at 28 days and 90 days. |
-Aumento en el aclaramiento de lactato a las 6, 24 y 72 horas de la administración de terlipresina/placebo. -Incremento de los días con vida libres de ventilación mecánica medidos a los 28 días. -Incremento de los días con vida libres de vasopresores medidos a los 28 días. -Mortalidad a los 28 días y a los 90 días. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |