E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intensive Care patients with the systemic inflammatory response syndrome |
Intensive Care patienten met een systemisch inflammatoir response syndroom |
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E.1.1.1 | Medical condition in easily understood language |
Intensive Care patients with a systemic inflammation |
Intensive Care patienten met een systemische ontstekingsreactie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062357 |
E.1.2 | Term | SIRS |
E.1.2 | System Organ Class | 100000004867 |
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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 study the short- and long-term effect of different PaO2 targets on circulatory status, organ dysfunction and outcome. |
Het onderzoeken van de korte en lange termijn effecten van verschillende streef zuurstofwaarden op circulatie, orgaan dysfunctie en overleving. |
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E.2.2 | Secondary objectives of the trial |
To study underlying mechanisms of hyperoxia by determining differences in oxidative stress response between the hyperoxic patients and the normoxemic groups.
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Het onderzoeken van e onderliggende mechanismen van hyperoxie door het bepalen van verschillen in oxidatieve stress tussen patienten met hyperoxie en normoxie. |
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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 |
To further investigate the circulatory changes due to differences in oxygen suppletion, we will study additional parameters in a subgroup of 40 patients, which are too time-consuming to be performed in the whole group. We will estimate hemodynamics by PICCO (C.I., SVRI, extravascular lung water), microcirculation by sublingual Sidestream Dark Field imaging, and body fluid status by bio-impedance.
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In 40 patienten zullen we de circulatie intensiever onderzoeken (deze onderzoeken zijn te tijdrovend om bij de gehele groep te doen): -hemodynamiek door PICCO (C.I., SVRI, extravasculair long water), -microcirculatie met sublinguale Sidestream Dark Field imaging -vochtbalans met bio-impedantie.
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E.3 | Principal inclusion criteria |
-Age ≥18 years -≥2 positive SIRS-criteria: Temperature >38oC or hypothermia <36oC Heart rate >90 bpm Respiratory rate >20 /min or pCO2 <32 mmHg (4.3 kPa) Number of leucocytes >12 x 109/l of <4 x 109/l of >10% bands -Within 12 hours of admittance to the ICU -Expected stay of more than 48 hours as estimated by the attending physician
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-Leeftijd ≥18 jaar -≥2 positieve SIRS-criteria: Temperatuur >38oC of hypothermie <36oC Hart frequentie >90 bpm Ademhalingsfrequentie >20 /min of pCO2 <32 mmHg (4.3 kPa) Aantal leucocyten >12 x 109/l of <4 x 109/l of >10% staven -Binnen 12 uur van opname op de IC -Verwachte verblijfsduur van > 48 uur zoals ingeschat door de behandelend arts
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E.4 | Principal exclusion criteria |
-Elective surgery -Carbon monoxide poisoning -Cyanide intoxication -Methemoglobinemia -Pregnancy -Severe COPD (Gold class III or IV) or other sever chronic pulmonary disease -Sickle cell anemia -Known pulmonary arterial hypertension (WHO class III or IV) -Known cardiac right to left shunting |
-Electieve chirurgie -Koolmonoxide vergiftiging -Cyanide intoxicatie -Methemoglobinemie -Zwangerschap -Ernstige COPD (Gold class III of IV) of andere ernstig chronisch longlijden -Sikkelcelanemie -Pulmonale arteriele hypertensie (WHO klasse III of IV) -Cardiale rechts-links shunting |
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E.5 End points |
E.5.1 | Primary end point(s) |
The cumulative Δ Sequential Organ Failure (SOFA) score within the first 14 days of inclusion |
De cumulatieve Δ Sequential Organ Failure (SOFA) score gedurende de eerste 14 dagen |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
First 14 days |
Eerste 14 dagen |
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E.5.2 | Secondary end point(s) |
Secondary parameters will include time spent in the assigned PaO2 range, hypoxic episodes (PaO2 <55 mmHg), vasopressor / inotrope requirements (max dose every 24 hours), need for renal replacement therapy and fluid balances (every 24 hours). Furthermore, oxidative stress parameters F2-isoprostanes will be determined (on day 1, 2 and 4) and as clinical endpoints: duration of mechanical ventilation, lung injury score, ventilator-free days, length of stay (in ICU, in hospital) and mortality (ICU and hospital). |
Secondaire parameters: tijd binnen streef PaO2 bereik, hypoxische episodes (PaO2 <55 mmHg), vasopressor / inotropie behoeften (max dosis elke 24 uur), noodzaak tot nierfunctievervangende therapie, vochtbalans (elke 24 uur). Oxidatieve stress parameters F2-isoprostanes op dag 1, 2 en 4) en als klinische eindpunten: duur beademing, lung injury score, ventilator-vrije dagen, ligduur IC en in ziekenhuis, mortaliteit (IC en ziekenhuis). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
First 14 days |
Eerste 14 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 | No |
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 | 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) | 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 | No |
E.8.1.3 | Single blind | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Andere streefwaarde van PaO2 |
Other target range of PaO2 |
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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 | 3 |
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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LVLS |
Nadat 400 patienten geincludeerd zijn |
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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 | |
E.8.9.1 | In the Member State concerned days | |