E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe sepsis and septic shock |
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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 |
To investigate the clinical efficacy on 28 day all cause mortality and survival rate of a high and a low dosage of iv Alkaline Phosphatase (AP) in comparison to placebo in patients with severe sepsis and septic shock |
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of a high and low dosage of AP in comparison to placebo in patients with severe sepsis and septic shock, on clinical efficacy variables like: • Day 28 clinical condition • Per patient variable: Change from baseline of APACHE II- score and SOFA score. ICU and hospital length of stay. Number of days on mechanical ventilation and/or extra-renal support. To investigate the effect of a high and low dosage of AP in comparison to placebo in patients with severe sepsis and septic shock, on surrogate efficacy variables like: Per patient change from baseline of: Inflammation variables. Pharmacokinetics. Immunological variables. To investigate the safety and tolerability of a high and low AP dosage in comparison to placebo, in patients with severe sepsis and septic shock
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Clinical defined sepsis: • Proven or suspected bacterial infection and • Minimally 2 out of 4 SIRS criteria of systemic inflammation positive: Acute onset of at least 1 end-organ dysfunction in the preceding 36 hours: • unrelated to the primary septic focus and • not explained by any underlying primary chronic disease and • as described by at least one of the following 7 underlying conditions: 1. Sustained hypotension 2. Acute renal failure 3. Acute alteration in mental state 4. Acute hypoxemic respiratory failure 5. Disseminated intravascular coagulopathy (DIC) 6. Metabolic acidosis 7. Acute hepatic failure at least 18 years Body weight ≤ 125 kg Being committed to - and treated with full intensive care support Written informed consent obtained.
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E.4 | Principal exclusion criteria |
1. Patients being treated for transplantation of bone marrow, lung, liver, pancreas or other condition. 2. Known confirmed gram-positive sepsis. 3. Known confirmed fungal sepsis. 4. Chronic renal failure requiring hemodialysis or peritoneal dialysis. 5. Acute pancreatitis with no established source of infection. 6. Patients expected to have rapidly fatal disease within 24 hours . 7. Patients not expected to survive for 28 days, due to other medical conditions such as end-stage neoplasm or other diseases. 8. Patients being treated with cancer related chemotherapy. 9. Participation in another investigational study which clearly and documented interferes with this study, within 30 days prior to start of the study . 10. Previous administration of AP. 11. Allergy for cow milk. 12. Known HIV patients with CD4-count < 50. 13. Pregnant and lactating women. |
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E.5 End points |
E.5.1 | Primary end point(s) |
28 day all cause mortality and survival rate |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | No |
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 | 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) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 2 |
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 |