E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Septic shock |
Shock settico |
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E.1.1.1 | Medical condition in easily understood language |
Septic shock |
Shock settico |
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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 | 20.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In the current study, in patients with septic shock, we aim to investigate whether: 1) albumin in addition to crystalloids vs crystalloids alone reduces 90-day mortality (Aim 1); 2) BAL solutions reduces 90-day mortality and/or the incidence of AKI as compared to normal saline (NS) (Aim 2). |
Nel presente studio, in pazienti con shock settico, ci proponiamo di studiare se: 1) la somministrazione di albumina in aggiunta a cristalloidi, rispetto all’utilizzo dei soli cristalloidi riduce la mortalità a 90 giorni (Obiettivo 1); l’utilizzo di soluzioni cristalloidi bilanciate (BAL) riduce la mortalità a 90 giorni o l’incidenza di insufficienza renale acuta, rispetto all’utilizzo di Soluzione Fisiologica (NS) (Obiettivo 2). |
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E.2.2 | Secondary objectives of the trial |
Aim 1 • ICU mortality • In-hospital mortality • 1-year mortality • Severity and incidence of organ failures, as assessed by the SOFA score • Incidence of AKI, as assessed by the KDIGO criteria • Use of renal replacement therapy (RRT) during ICU stay • Duration of the need for vasopressors during ICU stay • Duration of mechanical ventilation during ICU stay • Incidence of secondary-acquired infections during ICU stay • Length of stay in ICU • Length of stay in Hospital Aim 2 • 90-day mortality • Incidence of AKI, as assessed by the KDIGO criteria • ICU mortality • In-hospital mortality • 1-year mortality • Severity and incidence of organ failures, as assessed by the SOFA score • Use of renal replacement therapy (RRT) during ICU stay • Incidence of severe metabolic acidosis • Incidence of severe hyperkalemia • Duration of mechanical ventilation • Length of stay in ICU • Length of stay in Hospital
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Obiettivo 1 • Mortalità in Terapia Intensiva • Mortalità intra-ospedaliera • Mortalità a 1 anno • Gravità e incidenza di insufficienze d’organo, valutate con SOFA • Incidenza di insufficienza renale acuta, valutata secondo i criteri KDIGO • Uso di tecniche di depurazione renale durante degenza in Terapia Intensiva • Durata della necessità di farmaci vasopressori durante degenza in Terapia Intensiva • Durata della ventilazione meccanica durante degenza in Terapia Intensiva • Incidenza di infezioni secondarie acquisite, durante degenza in Terapia Intensiva • Durata della degenza in Terapia Intensiva • Durata della degenza ospedaliera Obiettivo 2 • Mortalità a 90 giorni • Incidenza di insufficienza renale acuta, valutata secondo i criteri KDIGO • Mortalità in Terapia Intensiva • Mortalità intra-ospedaliera • Mortalità a 1 anno • Gravità e incidenza di insufficienze d’organo, valutate con SOFA • Uso di tecniche di depurazione renale durante degenza in Ti • Durata ospedalizzazione |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be enrolled if they meet the two following criteria: 1) Presence of an infection (known or suspected) in at least one site: a) Lung b) Abdomen c) Urinary tract d) Others (blood, skin and soft tissues, central nervous system, bones and joints, cardiac system, reproductive organs) 2) Presence of a severe and acute, sepsis-related cardiovascular failure, requiring vasopressor to maintain mean arterial pressure >= 65 mmHg, despite adequate volume resuscitation a) Cardiovascular SOFA score > 2 (3 or 4) |
1) Presenza di una certa o sospetta infezione in almeno una sede: a) Polmone b) Addome c) Trattogenito-urinario d) Altro (sangue, tessuti molli, sistema nervoso centrale, apparato osteoarticolare, sistema cardiaco, organi riproduttivi) 2) Presenza di una grave ed acuta insufficienza cardiovascolare sepsi-correlata, necessitante l’utilizzo di farmaci vasopressori per mantenere una pressione arteriosa media>= 65 mmHg, nonostante un adeguato rimpiazzo volemico. a) Punteggio cardiovascolare SOFA > 2 (3 o 4)
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E.4 | Principal exclusion criteria |
1)Age < 18 years 2)Moribund state 3)Known or suspected adverse reaction to albumin administration 4)Severe sepsis or septic shock in patients with traumatic brain injury or a clinically active cerebral lesion (known or suspected) 5) Severe congestive heart failure (NYHA III and IV classes) 6) Clinical situations in which the use of albumin is known or supposed to be clinically effective (hepatic cirrhosis with ascites, malabsorption syndrome or protein-losing enteropathy, nephrotic syndrome, burns) 7) More than 24 hours after the onset of septic shock 8) Religious objection to the administration of human blood products 9) Presence of chronic end-stage renal disease 10)Severe hyperkalemia 11)Enrollment in other experimental studies |
1) Età inferiore ai 18 anni 2) Stato terminale 3) Reazione allergica nota o sospetta alla somministrazione di albumina 4) Shock settico in pazienti con trauma cerebrale o lesione cerebrale nota o sospetta, clinicamente attiva 5) Severa Insufficienza cardiaca congestizia (classe NYHA III e IV) 6) Situazioni cliniche in cui l’utilizzo di albumina è di provata o supposta efficacia clinica (cirrosi epatica ascitogena, sindrome da malassorbimento o da proteino-dispersione intestinale, sindrome nefrosica, ustioni estese) 7) Passate più di 24 ore dall’insorgenza dello shock settico 8) Obiezione religiosa alla somministrazione di emocomponenti umani 9) Presenza di insufficienza renale cronica terminale 10) Grave iperkalemia 11) Inclusione in altri studi sperimentali
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E.5 End points |
E.5.1 | Primary end point(s) |
All-cause 90-day mortality (Aim 1), and a combined primary endpoint including 90-day mortality and/or incidence of AKI during the study (Aim 2). |
Mortalità per ogni causa a 90 giorni (Obiettivo 1), e la combinazione di mortalità per ogni causa a 90 giorni e/o l’incidenza di insufficienza renale acuta durante lo studio (Obiettivo 2). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Aim 1 • ICU mortality • In-hospital mortality • Severity and incidence of organ failures, as assessed by the SOFA score • Incidence of AKI, as assessed by the KDIGO criteria • Use of renal replacement therapy (RRT) during ICU stay • Duration of the need for vasopressors during ICU stay • Duration of mechanical ventilation during ICU stay • Incidence of secondary-acquired infections during ICU stay • Length of stay in ICU • Length of stay in Hospital Aim 2 • 90-day mortality • Incidence of AKI, as assessed by the KDIGO criteria • ICU mortality • In-hospital mortality • Severity and incidence of organ failures, as assessed by the SOFA score • Use of renal replacement therapy (RRT) during ICU stay • Incidence of severe metabolic acidosis • Incidence of severe hyperkalemia • Duration of mechanical ventilation • Length of stay in ICU • Length of stay in Hospital
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Obiettivo 1 • Mortalità in Terapia Intensiva • Mortalità intra-ospedaliera • Gravità e incidenza di insufficienze d’organo, valutate con il punteggio SOFA • Incidenza di insufficienza renale acuta, valutata secondo i criteri KDIGO • Uso di tecniche di depurazione renale durante degenza in Terapia Intensiva • Durata della necessità di farmaci vasopressori durante degenza in Terapia Intensiva • Durata della ventilazione meccanica durante degenza in Terapia Intensiva • Incidenza di infezioni secondarie acquisite, durante degenza in Terapia Intensiva • Durata della degenza in Terapia Intensiva • Durata della degenza ospedaliera Obiettivo 2 • Mortalità a 90 giorni • Incidenza di insufficienza renale acuta, valutata secondo i criteri KDIGO • Mortalità in Terapia Intensiva • Mortalità intra-ospedaliera • Gravità e incidenza di insufficienze d’organo, valutate con il punteggio SOFA • Uso di tecniche di depurazione renale durante degenza in Terapia Intensiva • Incidenza di grave acidosi metabolica • Incidenza d grave iperkalemia • Durata della ventilazione meccanica durante degenza in Terapia Intensiva • Durata della degenza in Terapia Intensiva • Durata della degenza ospedaliera
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
• Ringer Lattato • Ringer Acetato • Crystalsol • Normal Saline (Na+ 154 mEq/L, Cl– 154 mEq/L) |
• Ringer Lactate • Ringer Acetate • Crystalsol • Normal Saline (Na+ 154 mEq/L, Cl– 154 mEq/L) |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 42 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 0 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |