E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with septic shock admitted to the intensive care unit. |
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E.1.1.1 | Medical condition in easily understood language |
Overwhelming response to a blood stream infection causing life threatening drop in blood pressure necessitating admission to the intensive care unit. |
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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 | 19.1 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy of OctaplasLG® administration as compared to crystalloids (standard of care) in patients with septic shock |
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E.2.2 | Secondary objectives of the trial |
Safety of OctaplasLG®administration as compared to crystalloids (standard of care) in patients with septic shock |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria 1. Adult intensive care patients (age ≥ 18 years) AND 2. Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection AND 3. Quick SOFA (qSOFA) with two or more of a. Respiratory rate ≥ 22/min b. Altered mentation (Glasgow Coma Scale score < 15) c. Systolic blood pressure ≤ 100mmHg AND 4. Septic shock, defined as a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L despite adequate volume resuscitation AND 5. Requiring infusion of noradrenalin 0.10 mcg/kg/min or more to maintain blood pressure AND 6. Respiratory failure requiring intubation and mechanical ventilation |
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E.4 | Principal exclusion criteria |
Exclusion criteria Patients are not eligible for inclusion in this trial if they fulfil one or more of the following criteria: 1. Documented refusal of blood transfusion OR 2. Treatment with GPIIb/IIIa inhibitors < 24h from screening OR 3. Withdrawal from active therapy OR 4. Known IgA deficiency with documented antibodies against IgA OR 5. Known hypersensitivity to OctaplasLG®: the active substance, any of the excipients (Sodium citrate dihydrate, Sodium dihydrogenphosphate dihydrate or Glycine) or residues from the manufacturing process (Tri (N-Butyl) Phosphate (TNBP) and Octoxynol (Triton X-100)) OR 6. Known severe deficiencies of protein S OR 7. Pregnancy (non-pregnancy confirmed by patient being postmenopausal or having a negative urine-hCG) OR 8. Previously within 30 days included in an interventional trial OR 9. Severe cirrhotic hepatic failure with expected need for treatment with terlipressin |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints • Change in microvascular perfusion from baseline to 24 hours after inclusion as evaluated by sidestream darkfield (SDF; MicroVision Medical, Amsterdam, The Netherlands) imaging technique. • Change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, thrombomodulin, VEGFR1, VEGF, nucleosomes) from baseline to 24 hours after inclusion. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 hours after inclusion in the trial as compared to baseline (inclusion) |
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E.5.2 | Secondary end point(s) |
Secondary endpoints • Difference in 24 hours, 7, 30 and 90 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids, such as Ringer-Acetate) • Length of stay in the ICU • Days on vasopressors (without vasopressors in ICU) • Days on ventilator (of ventilator-free days in ICU) • Bleeding requiring > 2 RBC / day during the first 7 days • Severe adverse reactions, defined as symptomatic thromboembolism and TACO/TRALI during the first 72 hours and at day 30. • Oxygenation as evaluated by the PaO2/FiO2-ratio during the ICU stay • Acute Kidney Injury (AKI) according to RIFLE Criteria during the first 7 ICU days • Renal replacement therapy, as deemed necessary by the attending physician, during the first 7 days post-randomization.
Safety endpoints • Maximal change in SOFA score from baseline to 24, 48 and 72 hours as well as at ICU day 7. • Thrombelastograph maximum amplitude (clot strength) in TEG and Functional Fibrinogen (FF) at 24, 48 and 72 hours as compared to baseline. • Disseminated intravascular coagulation score (DIC) at 24, 48 and 72 hours as well as at ICU day 7. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Difference in 24 hours, 7, 30 and 90 day mortality between patients receiving active treatment (OctaplasLG®) and standard of care (crystalloids) Other secondary and safety endpoint during the first 72 hours and at day 7 and 30.
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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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The trial will end on April 1, 2020 to compensate for the 90 day follow up period for each included patient as well as the biomarker analysis. |
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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 | 17 |