E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Shock-induced endotheliopathy in patients with septic shock |
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E.1.1.1 | Medical condition in easily understood language |
Septic patients with shock and damage to the smallest blood vessels |
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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 | 20.0 |
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 |
The main objective in this trial is to investigate whether continuous infusion of iloprost at a dose of 1 ng/kg/min for 72-hours is safe and significantly reduce organ failure score in the ICU compared to infusion of placebo in patients with septic shock and SHINE. |
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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 |
1. Adult intensive care patients (age ≥ 18 years)
2. Septic shock, defined as (i) suspected or documented infection, (ii) persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg AND a lactate level >2 mmol/L despite fluid therapy
3. sTM > 10 ng/mL
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E.4 | Principal exclusion criteria |
1. Withdrawal from active therapy
2. Pregnancy (non-pregnancy confirmed by patient having a negative urine- or plasma hCG or being postmenopausal defined as females at 60 years old and beyond or at the investigators discretion)
3. Known hypersensitivity to iloprost or to any of the other ingredients.
4. Life-threatening bleeding as defined by the treating physician
5. Known severe heart failure (NYHA class IV)
6. Suspected acute coronary syndrome
7. Previously included in this trial
8. Screening > 12 hours after diagnosis of septic shock
9. Informed consent cannot be obtained
10. Included in clinical trials with prostacyclin within the last 90 days |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean daily modified Sequential Organ Failure Assessment (SOFA) score, involving respiration-, coagulation-, liver-, cardiovascular- and renal function in the intensive care unit up to day 90 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; the maximum score is 20) |
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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) |
• 28 and 90-day mortality
• Vasopressor-free days in the ICU within 90 days
• Ventilator-free days in the ICU within 90 days
• Renal replacement free days in the ICU within 90 days
• Numbers of serious adverse reactions within the first 7 days
• Numbers of serious adverse events within the first 7 days (SAE is defined as ischaemic events and bleeding events (defined as requiring > 2 RBCs within 24 hours or ongoing bleeding)).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | Yes |
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 | 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 | 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
| 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 | 5 |
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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Day 90 after inclusion of last patient |
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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 | |
E.8.9.2 | In all countries concerned by the trial years | 3 |