E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Sepsis with severe circulatory impairment |
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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 | 17.0 |
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 |
to assess the feasibility of a trial comparing two approaches to fluid resuscitation of septic shock after initial resuscitation; a trigger guided approach vs. a target guided approach, the latter reflecting standard care |
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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 |
Adult intensive care patients (age ≥ 18 years) with sepsis defined as 2 of 4 SIRS criteria fulfilled within 24 hours and suspected or confirmed site of infection or positive blood culture AND Suspected or confirmed circulatory impairment (hypotension/hypoperfusion/hypovolemia) for at least 6 hours and no more than 12 hours including the hours preceding ICU admission AND At least 30 ml/kg IBW fluid (colloids, crystalloids or blood products) given in the last 6 hours AND Shock (defined as ongoing infusion of norepinephrine (any dose) to maintain blood pressure)
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E.4 | Principal exclusion criteria |
Use of any form of renal replacement therapy (RRT) or RRT deemed imminent by the ICU doctor, i.e. RRT will be initiated within 6 hours. Severe hyperkalemia (p-K > 6 mM). Plasma creatinine > 350 µmol/l. invasively ventilated with FiO2 > 0.80 and PEEP > 10 mmHg. Life-threatening bleeding. Kidney or liver transplant during current admission. Burns > 10% BSA. Previously enrolled in the CLASSIC trial and has finished the 90 day observation period Withdrawal of active therapypatients for whom it has been decided not to give full life support including mechanical ventilation and RRT. Consent not obtainable. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Amount of resuscitation fluid given in the first 5 days after randomisation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
day 5 after randomisation |
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E.5.2 | Secondary end point(s) |
Secondary outcomes: 2.1 Amount of resuscitation fluid given during ICU stay 2.2 Fluid balance and total fluid input at day 5 after randomisation and during ICU stay 2.3 Number of patients with major protocol violations 2.4 Accumulated serious adverse reactions (SARs) in ICU Exploratory outcomes: a. All-cause mortality at day 90 b. Mortality during the total observation time c. Days alive without use of mechanical ventilation d. Days alive without use of RRT e. Worsening of acute kidney injury according to KDIGO criteria during ICU stay f. Delta-creatinine (defined as highest p-creatinine during ICU stay minus most recent p-creatinine prior to randomisation) g. Ischaemic events in ICU.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 5 after randomisation, ICU discharge or 90 days after randomisation |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
feasibility of the Protocol |
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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 |
Different approach to 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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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The trial will end when number of randomised patients reach 150 |
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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 | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |