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 |
Inability of the circulatory system to maintain a normal blood pressure and cellular respiration |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
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 primary objective of the study is to assess whether the normalization of peripheral perfusion with nitroglycerin therapy during resuscitation of patients with circulatory shock will improve ICU mortality. |
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E.2.2 | Secondary objectives of the trial |
To assess nitroglycerin therapeutic effect on the 28-day mortality, APACHE II, SOFA, length of stay in the ICU, mechanical ventilation free-days, renal replacement therapy, vasopressors and inotropics use. Additional secondary objective is to investigate which peripheral vascular bed (skin, muscle, gastrointestinal mucosa) contributes most to tissue hypoperfusion in shock and its mortality.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All consecutive adult patients admitted to the intensive care for circulatory shock resuscitation in whom abnormal peripheral perfusion is still present despite normalization of global hemodynamic parameters are eligible for this study. |
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E.4 | Principal exclusion criteria |
Liver failure, severe coagulation disorder, and any neurological insult that could lead to increased intracranial pressure (stroke, subarachnoid haemorrhage, brain trauma injury). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end-point is improvement in peripheral perfusion defined as a change of more than 50% in baseline peripheral perfusion parameters (capillary refill time or the presence of peripheral vasodilation: body temperature gradient <2 ºC and peripheral perfusion index >1.4 %). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Peripheral perfusion measurements will be performed each 15 minutes until improvement is observed. Additional measurements will be performed after 8h, 16h and 24h of nitroglycerin infusion. Peripheral perfusion parameters, such as gastric tonometry and StO2 will also be recorded continuously for 72h. Sublingual microcirculation and StO2-derived vascular occlusion test will be performed before and after resuscitation protocol, and subsequently at 24, 48 and 72 hours. |
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E.5.2 | Secondary end point(s) |
Global hemodynamic parameters: Fluid balance, mean arterial pressure (MAP), central venous pressure (CVP), central venous oxygen saturation (ScvO2), cardiac output and stroke volume, lactate clearance.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Each 15 minutes until improvement in peripheral perfusion parameters is observed. |
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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 | 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 | 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 |
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E.8.2.4 | Number of treatment arms in the trial | 40 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |