E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Septic shock |
Septinen sokki |
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E.1.1.1 | Medical condition in easily understood language |
Sepsis with severe circulatory impairment |
Vakava verenkierronhäiriö septisessä sokissa |
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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 | LLT |
E.1.2 | Classification code | 10040050 |
E.1.2 | Term | Sepsis NOS |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The objective of the CLASSIC trial is to assess benefits and harms of IV fluid restriction vs. standard of care on patient-important outcome measures in adult ICU patients with septic shock. |
CLASSIC tutkimuksessa selvitetään hyötyjä ja haittoja koskien rajoitettua suonensisäistä nestehoitoa vertailemalla normaaliin nestehoitoon tehohoitopotilailla, joilla on septinen sokki. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All the following criteria must be fulfilled:
- Aged 18 years or above
- Admitted to the ICU or plan to be admitted to the ICU regardless of trial participation
- Septic shock defined according to the Sepsis-3 criteria:
o Suspected or confirmed site of infection or positive blood culture AND
o Ongoing infusion of vasopressor/inotrope agent to maintain a mean arterial blood pressure of 65 mmHg or above AND
o Lactate of 2 mmol/L or above in any plasma sample performed within the last 3-hours
- Have received at least 1 L of IV fluid (crystalloids, colloids or blood products) in the last 24-hours prior to screening.
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Sisäänottokriteerit:
- ≥ 18 vuotias
- Tarvitsee tehohoitoa tutkimukseen osallistumisesta huolimatta
- Septinen sokki SEPSIS-3 kriteereiden mukaisesti:
--> Epäily tai todettu infektio tai positiivinen veriviljely löydös JA
--> Jatkuva vasopressori/inotropia infuusio, jotta keskiverenpaine on ≥ 65 mmHg JA
--> Laktaatti ≥ 2 mmol/L viimeisen kolmen tunnin aikana
- Saanut vähintään 1 L iv nesteitä (kristalloideja, kolloideja tai verituotteita) viimeisen 24 tunnin aikana ennen arviointia tutkimukseen. |
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E.4 | Principal exclusion criteria |
We will exclude patients who fulfil any of the following criteria:
- Septic shock for more than 12 hours at the time of screening because we want to include patients early in their course
- Life-threatening bleeding as these patients need specific fluid/blood product strategies
- Acute burn injury of more than 10% of the body surface area as these patients need a specific fluid strategy
- Known pregnancy.
- Consent not obtainable as per the model approved for the specific site.
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Poissulkukriteerit:
- Septinen sokki yli 12 tuntia tutkimuksen arvioinnista koska potilaat halutaan inkludoida tutkimukseen mahdollisimman varhaisessa vaiheessa.
-Henkeä uhkaava verenvuoto, jolloin potilas tarvitsee erityistä neste/verituote hoitoa.
-Yli 10% kehon pinta-alaa koskeva akuutti palovamma jolloin potilas tarvitsee erityistä nestehoitoa.
-Raskaus.
-Tutkimuslupaa ei ole mahdollista saada keskukselle hyväksytyllä tavalla. |
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E.5 End points |
E.5.1 | Primary end point(s) |
All-cause mortality at day 90 after randomisation |
Kuolleisuus 90 päivää randomisaation jälkeen. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
day 90 after randomisation |
90 päivää randomisaatiosta |
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E.5.2 | Secondary end point(s) |
- Number of participants with one or more serious adverse events (SAEs) in the ICU defined as ischaemic events (cerebral, cardiac, intestinal or limb ischaemia) or as a new episode of severe acute kidney injury (modified KDIGO3)
- Number of participants with one or more serious adverse reactions (SARs) to IV crystalloids in the ICU.
- Days alive at day 90 without life support (vasopressor / inotropic support, invasive mechanical ventilation or renal replacement therapy)
- Days alive and out of hospital at day 90
- All-cause mortality at 1-year after randomisation
- HRQoL 1-year after randomisation measured using the EuroQoL (EQ)-5D-5L and EQ-VAS scores. Participants who have died will be assigned the lowest possible scores
- Cognitive function 1-year after randomisation as assessed by the Montreal Cognitive Assessment (MoCa) score
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- Tutkittavien potilaiden määrä tehohoidossa, joilla on vähintään yksi vakava haittatapahtuma (SAE) määritelmänä iskeeminen tapahtuma (iskeeminen aivotapahtuma, sydänlihasiskemia, suolistoiskemia tai raajaiskemia) tai uutena tapahtumana vakava akuutti munuaisten vajaatoiminta (KDIGO3 mukaan).
- Tutkittavien potilaiden määrä tehohoidossa, joilla on vähintään yksi vakava haittareaktio (SAR) IV kristallodille.
- Elossaolopäivät 90 päivän kohdalla ilman tukihoitoa (vasopressori/inotropia tukea, hengityslaitehoitoa tai munuaiskorvaushoitoa)
- Elossaolopäivät sairaalan ulkopuolella 90 päivän aikana.
- Kuolleisuus vuoden kuluttua randomisaatiosta.
- Elämänlaatukysely vuoden kuluttua randomisaatiosta käyttäen EuroQol-5D-5L ja EQ-VAS pisteytystä. Tutkittavat jotka ovat kuolleet arvioidaan huonommalla mahdollisella pisteytyksellä.
- Kongnitiivinen toiminto vuoden kuluttua randomisaatiosta Montreal Cognitive Assessment (MoCa) pisteillä arvioituna. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
during ICU admission, day 90 after randomisation or 1 year after randomisation |
Teholla sisäänkirjattuna, 90 päivää randomisaation jälkeen tai vuoden jälkeen randomisaatiota. |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
fluid resuscitation reflecting standard care |
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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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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The trial will end when number of randomised patients reach 1554 |
Tutkimus päättyy kun siihen on randomoitu kaikkiaan 1554 potilasta ja heidän kunkin jatkoseuranta aina vuoteen asti on tehty. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |