E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients admitted to the Intensive Care after out-of-hospital cardiac arrest with return of spontaneous circulation, ventricular fibrillation or ventricular tachycardia as first registered cardiac rhythm and EMV-score ≤8 |
Patiënten opgenomen op de Intensive Care na een reanimatie buiten het ziekenhuis met herstel van spontane circulatie, ventrikel fibrilleren of ventrikel tachycardie als eerste geregistreerde ritme en een EMV-score ≤8 |
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E.1.1.1 | Medical condition in easily understood language |
Patients admitted to the Intensive Care after after cardiopulmonary resuscitation who remain comatose |
Patiënten opgenomen op de Intensive Care na een reanimatie buiten het ziekenhuis die buiten bewustzijn blijven |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 | 10078202 |
E.1.2 | Term | Post cardiac arrest syndrome |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 determine whether an early high dose i.v. vitamin C can improve organ function, especially neurological outcome, in patients after cardiac arrest
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- Kan een vroeg toegediende, hoge dosis i.v. vitamine C orgaan functie (in het bijzonder neurologische uitkomst), verbeteren in patienten na reanimatie?
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E.2.2 | Secondary objectives of the trial |
- To explore the optimal dosing regimen for high dose i.v. vitamin C - To investigate in vitro the difference in effect of plasma obtained from post cardiac arrest patients treated with placebo, 3 gr/day or 10 gr/day vitamin C on endothelial cell viability and underlying oxidative pathways.
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- Indien vitamine C orgaanfunctie verbetert, werkt 3 gr/dag dan beter dan 10 gr/dag? - Is er in vitro verschil in effect van het plasma van de studiepatiënten op endotheliale celdood en wat zijn de onderliggende oxidatieve mechanismen?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients suffering an out-of-hospital cardiac arrest with return of spontaneous circulation, ventricular fibrillation or ventricular tachycardia as first registered cardiac rhythm and EMV-score ≤8 will be included. |
Patiënten op de Intensive Care opgenomen na een reanimatie buiten het ziekenhuis met herstel van spontane circulatie, ventrikel fibrilleren of ventrikel tachycardie als eerste geregistreerde ritme en een EMV-score ≤8 zullen worden geincludeerd. |
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E.4 | Principal exclusion criteria |
Patients with pre-existent terminal renal insufficiency (i.e. receiving renal replacement therapy (RRT)), known glucose 6-phosphate dehydrogenase deficiency (risk of hemolysis), history of urolithiasis, oxalate nephropathy, hemochromatosis or treatment limitations will be excluded. |
Patiënten met in de voorgeschiedenis pre-existente terminale nierinsufficiëntie (d.w.z. het ontvangen van nierfunctie vervangende therapie), glucose 6-phosphate dehydrogenase deficientie (risico op hemolyse), urolithiasis, oxalate nefropathie, hemochromatose of behandel beperkingen zullen worden geexcludeerd. |
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E.5 End points |
E.5.1 | Primary end point(s) |
We will determine organ failure at 96 hours measured by the delta (Δ) Sequential Organ Failure Assessment (SOFA) score. ΔSOFA score is defined as the difference between SOFA admission and SOFA at 96 hour. Death at 96-hours will be counted as the maximum SOFA score (24 points). |
We onderzoeken orgaanfalen na 96 uur gekwantificeerd door de delta (Δ) Sequential Organ Failure Assessment (SOFA) score. ΔSOFA score is gedefinieerd door het verschil tussen SOFA bij opname en SOFA na 96 uur. Overleden na 96 uur zal berekend worden als de maximale SOFA score (24 punten). |
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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) |
As secondary outcomes we will investigate: neurological outcome (Maximal Glasgow Coma Score at 96-h and and the end of ICU-stay; Cerebral Performance Categories scale and Modified Rankin Scale at 30 and 180 days; HUI-3 questionnaire at 180 days; neuron-specific enolase day 1, 2 and 3); clinical parameters (IC- and hospital stay, 30-day and 90-day mortality), organ injury (myocardial injury measured by troponin and CK-MB (maximum day 1), lung injury score, ventilation time, renal function, need of renal replacement therapy, IC-acquired weakness (Medical Research Council score), delirium (CAM-ICU score), mitoPO2, oxidative stress parameters (such as F2-isoprostanes and oxidation reduction potential (ORP)), anti-oxidant capacity (AOC) and vitamin C plasma concentrations.
In vitro experiments: To determine the different effect of 3 or 10 gram vitamin C or placebo on the underlying oxidative pathways we will investigate how plasma obtained from the trial patients affects cultured human systemic microvascular endothelial cells with regard to endothelial cell viability, ROS production intracellular vitamin C concentrations, NADPH-oxidase expression, p47Phox expression, endothelial barrier function and mitochondrial respiratory chain function. |
Als secondaire uitkomstmaten zullen we onderzoeken: neurologische uitkomst (Maximale Glasgow Coma Score na 96 uur en aan het einde van de IC-opname; Cerebral Performance Categories scale en Modified Rankin Scale na 30 en 180 dagen, HUI-3 vragenlijst na 180 dagen; neuron-specific enolase dag 1, 2 en 3); klinische parameters (IC- en ziekenhuis ligduur, 30-dagen en 90-dagen mortaliteit), orgaan schade (myocardiale schade gemeten door troponine en CK-MB (maximum van dag 1), lung injury score, beademingsduur, nierfunctie, noodzaak tot nierfunctie-vervangende therapie, IC-acquired weakness (Medical Research Council score), delier (CAM-ICU score), mitoPO2, oxidatieve stress parameters (zoals F2-isoprostanen en oxidatie reductie potentiaal (ORP)), anti-oxidante capaciteit (AOC) en vitamine C plasma concentraties.
In vitro experimenten: om het verschil in effect te bepalen van 3 gr of 10 gr vitamine C per dag of placebo op de onderliggende oxidatieve mechanismen zullen we het effect onderzoeken van plasma verkregen van de trial patienten op gekweekte humane systemische microvasculaire endotheliale cellen met betrekking tot endotheliale cel overleving, ROS productie, intracellulaire vitamine C concentraties, NADPH-oxidase expressie, p47Phox expressie, endotheliale barriere functie en mitochondriale respiratoire keten functie. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 96 hours and at the end of ICU-stay. Neurological outcome will also be evaluated after 30 days and after 180 days. |
Na 96 uur en aan het einde van de IC-opname. Neurologische uitkomst zal ook onderzocht worden na 30 en 180 dagen. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Andere dosis |
Other dosage |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 9 |
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 | 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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When the last subject has finished his/her follow up of 180 days. |
Als de laatste patient gedurende 180 dagen gevolgd is. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |