E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Septic shock - low blood pressure due to infection |
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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 is to assess if corticosteroids increase circulating levels of vasopressin when used in the treatment of low blood pressure due to severe infection. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are 1) To assess if corticosteroids increase the blood pressure response to vasopressin treatment 2) To act as feasibility study for a larger double-blind randomised controlled trial to examine the optimal timimg and interaction of drugs currently used in the management of low blood pressure due to severe infection. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The target population is adult patients who require vasopressors for the management of sepsis despite fluid resuscitation. These patients will require management on the intensive care unit.
Inclusion criteria will use the internationally-established consensus definitions of sepsis. In brief:
• Fulfil 2/4 of the criteria of the systemic inflammatory response syndrome (SIRS) due to known or suspected infection within the previous 24 hours. The SIRS criteria are: (1) fever (>38° C) or hypothermia (< 36° C), (2) tachycardia (heart rate > 90 beats per minute), (3) tachypnea (respiratory rate > 20 breaths per minute or PaCO2 < 4.3 kPa) or need for mechanical ventilation, (4) abnormal leukocyte count (> 12,000 cells/mm3, < 4000 cells/mm3, or > 10% immature [band] forms).
• Hypotension despite adequate intravenous fluid resuscitation (minimum of 1 litre in the previous four hours).
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E.4 | Principal exclusion criteria |
• Patient has received a continuous infusion of vasopressors previously during this hospital admission (other than vasopressors used as emergency treatment to stabilise the patient during this episode). Vasopressors include noradrenaline, adrenaline, vasopressin, dopamine, metaraminol, phenylephrine.
• Regular systemic corticosteroid therapy within the previous three months (this does not include inhaled steroid therapy).
• End-stage renal failure
• Known adrenal dysfunction / insufficiency.
• Physician and team are not committed to full active care.
• Patient who is terminally ill (death anticipated within 24 hours).
• Patient is known to be pregnant.
• Patient has known acute mesenteric ischemia.
• Patient is being actively treated for an acute coronary syndrome.
• Patient is known to have Raynaud's phenomenon, systemic sclerosis or other vasospastic diseases.
• Patient is enrolled in another interventional trial that might interact with the study drugs.
• Patients has a history of anaphylaxis to any study drug.
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E.5 End points |
E.5.1 | Primary end point(s) |
Plasma vasopressin levels at 6-12 hours post study drug administration (eg hydrocortisone or placebo) between treatment groups. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
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 | Yes |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
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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When the last patient is discharged from hospital or day 28 whichever is later. This is 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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |