E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with severe sepsis or septic shock |
Pazienti con patologia chirurgica addominale severa; Pazienti con sepsi grave o shock settico |
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E.1.1.1 | Medical condition in easily understood language |
Patients with severe sepsis or septic shock |
Pazienti con patologia chirurgica addominale severa; Pazienti con sepsi grave o 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 | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066593 |
E.1.2 | Term | Post procedural sepsis |
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 | PT |
E.1.2 | Classification code | 10058040 |
E.1.2 | Term | Abdominal sepsis |
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 |
With this study we would evaluate the safety of pre-emptive therapy with LamB 5 mg/kg in the first 24h of treatment followed by LamB 3 mg/kg starting from the third day in patients with predefined high risk for IC/IAC. |
Obiettivo principale: Stabilire la sicurezza della terapia con LAmB 5 mg/kg nelle prime 24 ore di trattamento seguita da LAmB 3 mg/kg a partire dal 3 giorno nei pazienti con sospetta o confermata cadidiasi intraddominale invasiva (IAC). |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the cost-effectiveness of the use of BG in the management of antifungal therapy in patients with a severe surgical abdominal disease and severe sepsis or septic shock. 2. To assess the accuracy of BG for diagnosing IC/IAC in patients with severe abdominal surgical disease and severe sepsis or septic shock. 3. To investigate the outcome in terms of time to clinical stability, length of ICU and/or hospital stay, and rate of in-hospital mortality of the overall study cohort patients and in patients with IAC |
(i) Stabilire il rapporto cost-efficacia dell’utilizzo del Beta-D-glucano nella gestione della terapia antifungina in pazienti con IAC; (ii) Stabilire l’accuratezza del BD glucano nella diagnosi della IAC in pazienti con patologia addominale severa. (iii) Stabilire l’outcome, la durata della degenza e la mortalità nei pazienti arruolati nello studio. (v) stabilire il grado penetrazione tissutale di LamB e l’attività farmacodinamica nei pazienti con IAC (sottostudio di farmacocinetica/farmacodinamica condotto solo nel centro coordinatore) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies Specify title, date and version of each substudy with relative objectives: Title: A Pilot Substudy of Liposomal Amphotericin B Pharmacodynamics in Patients with Abdominal Sepsis” conducted only in the coordinating center
version 1.0 (14 june 2016)
Substudy is described in protocolo Lambda, sections: 12/3/14/15/
Substudy objective: To assess pharmacokinetics and pharmacodynamic activity of a 5 mg/kg LamB dose during the first 24 hours in a subset of 14 patients (substudy that will be conducted only in the coordinating center)
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Titolo: Sottotudio pilota di farmacodinamica di amfotericina B liposomiale in pazienti con sepsi addominale” che verrà condotto solo nel centro coordinatore
versione: 1.0 (14 giugno 2016);
Sottostudio è descritto nel documento Protocollo Lambda , capitoli 12/3/14/15/
Obiettivo di sottostudio: stabilire il grado penetrazione tissutale di LamB e l’attività farmacodinamica nei pazienti con IAC (sottostudio di farmacocinetica/farmacodinamica condotto solo nel centro coordinatore)
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E.3 | Principal inclusion criteria |
Inclusion criteria
1. All adult (= 18 years) patients 2. Patients with a severe surgical abdominal disease (SAD) defined as post-operative peritonitis, recurrent gastrointestinal perforation, post-operative hepatobiliary and pancreatic disorders, intra-abdominal abscess and anastomotic leak 3. Patients with severe sepsis or septic shock; 4. Signed informed consent |
Criteri di inclusione: i) età >18 anni; ii)Pazienti con patologia chirurgica addominale severa; iii)Pazienti con sepsi grave o shock settico ; iv)Firma del consenso informato |
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E.4 | Principal exclusion criteria |
Exclusion criteria
1. Patients with documented history of hypersensitivity or allergic reaction to liposomial amphotericin B 2. Pregnancy, lactation or patients at risk for pregnancy: premenopausal or postmenopausal woman within 12 months of last menses without negative pregnancy test or not committing to adequate birth control (e.g., oral contraceptive, two methods of barrier birth control). Diagnosis of pregnancy will be done using quantitative blood ß-HCG test. 3. Neutropenia > grade 2 defined as absolute neutrophils count = 1000/mmc 4. Concomitant treatment with cyclosporine, aminoglycosides and pentamidine |
Criteri di esclusione: i) Anamnesi documentata di ipersensibilità o reazione allergica ad amfotericina B; ii) gravidanza, allattamento o soggetto potenzialmente a rischio di gravidanza (mancato uso di contraccettivi orali o almeno due barriere fisiche al concepimento in soggetto in età fertile o con almeno un ciclo mestruale negli 12 mesi; test di gravidanza: beta-HCG test) iii) neutropenia superiore al grado 2 definita come conta di neutrofili = 1000/mmc; iv) utilizzo concomitante di ciclosporina, aminoglicosidi e pentamidina |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint:
Safety will be assessed according to the incidence of grade 3 to 4 adverse events (AEs) based on the Common Toxicity Criteria (CTC) classification, reported as definitely, possibly, or probably related to the study drug. The incidence of adverse events will be investigated from the initiation of the study drug until to 30 days after the study drug discontinuation. An iterim analysis will be performed after the enrollment of 19 patients. Only a rate of 10% of AEs will be acceptable (see sample size and iterim analysis section) |
L’endpoint primario dello studio è la sicurezza che verrà valutata attraverso l’incidenza degli eventi avversi di grado 3 e 4 secondo la classificazione common toxicity criteria (CTC). Il monitoraggio degli avventi avversi avverà dall’inizio del trattamento e proseguirà per 30 giorni dopo la sospensione |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 months (maximum 28 days of treatment and 30 days of follow-up after the end of treatment) |
2 mesi (massimo 28 giorni di trattamento e follow-up di 30 giorni dopo il termine di terapia) |
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E.5.2 | Secondary end point(s) |
1. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BG for diagnosing IC/IAC, established according to clinical and microbiological criteria, will be analyzed. 2. The time from severe sepsis or septic shock onset to clinical stability, the days of ICU and/or hospital stay and in-hospital all-cause mortality will be evaluated for all the enrolled patients and for patients with confirmed IC/IAC |
6.2 Secondary Endpoints:
- il tempo di stabilizzazione clinica dall’inizio della terapia antimicrobica, la mortalità a 30 giorni dalla diagnosi di SAD e la durata di degenza e di trattamento antifungino nei pazienti arruolati; -la sensibilità, la specifità, valore, predittivo positivo e negativo del BG nella diagnosi di IC/IAC |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 months (maximum 28 days of treatment and 30 days of follow-up after the end of treatment) |
2 mesi (massimo 28 giorni di trattamento e follow-up di 30 giorni dopo il termine di terapia) |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Studio NON controllato: sezione E.8.1: problema OsSC AIFA |
Studio NON controllato: sezione E.8.1: problema OsSC AIFA |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Studio NON controllato: sezione E.8.1: problema OsSC AIFA |
Studio NON controllato: sezione E.8.1: problema OsSC AIFA |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 8 |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 24 |
E.8.9.2 | In all countries concerned by the trial days | 0 |