E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vasopressor-dependent Septic Shock |
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E.1.1.1 | Medical condition in easily understood language |
Vasopressor-dependent Septic Shock |
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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 | 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 |
To demonstrate superiority of selepressin plus standard care versus placebo plus standard care in the number of vasopressor- and mechanical ventilator-free days (with penalty for mortality) in patients with vasopressor-dependent septic shock |
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E.2.2 | Secondary objectives of the trial |
To determine the efficacy of selepressin on:
- Organ dysfunction
- Morbidity and mortality
- Fluid balance
- Health-related quality of life
To determine the safety profile of selepressin
To determine the pharmacokinetics of selepressin
To determine the health economics of selepressin
To further evaluate a range of biomarkers in relation to the mode of action of selepressin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 18 years of age or older.
2. Proven or suspected infection.
3. Septic shock defined as hypotension (systolic blood pressure less than 90 mmHg OR MAP less than 65 mmHg) requiring vasopressor treatment (i.e. any dose of norepinephrine / noradrenaline greater than 5 μg/min) despite adequate fluid resuscitation (at least one litre for hypotension).
4. Informed consent obtained in accordance with local regulations. |
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E.4 | Principal exclusion criteria |
1. Not possible to initiate IMP treatment within 12 hours from onset of vasopressor treatment for septic shock.
2. Primary cause of hypotension not due to sepsis (e.g. major trauma including traumatic brain injury, haemorrhage, burns, or congestive heart failure/cardiogenic shock).
3. Previous severe sepsis with ICU admission within this hospital stay.
4. Known/suspected acute mesenteric ischaemia.
5. Suspicion of concomitant acute coronary syndrome based on clinical symptoms and/or ECG during this episode of septic shock.
6. Chronic mechanical ventilation for any reason OR severe chronic obstructive pulmonary disease (COPD) requiring either continuous daily oxygen use during the preceding 30 days or mechanical ventilation (for acute exacerbation of COPD) during the preceding 30 days.
7. Received bone marrow transplant during the preceding 6 months or chemotherapy during the preceding 30 days for lymphoma or leukemia.
8. Known to be pregnant.
9. Decision to limit full care taken before obtaining informed consent.
10. Use of vasopressin in the past 12 hours prior to start of the IMP infusion or use of terlipressin within 7 days prior to start of the IMP infusion.
11. Prior enrolment in the trial.
12. Prior use of an investigational medicinal product within the last month OR planned or concurrent participation in a clinical trial for any investigational drug or investigational device. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Vassopressor- and mechanical ventilator-free days (P&VFDs) up to Day 30 |
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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) |
- All-cause mortality (defined as the fraction of patients that have died, regardless of cause) at Day 90
- Renal replacement therapy (RRT)-free days up to Day 30 (excluding patients on RRT for chronic renal failure at time of randomisation)
- Intensive care unit (ICU)-free days up to Day 30 |
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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 | Yes |
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
two-part adaptive clinical trial |
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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 | 5 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
France |
Netherlands |
United States |
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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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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 | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |