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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
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 this study (MAP4B-safety) is to assess the safety of the application of the therapeutic product Alkaline Phosphatase (AP) in severely burned patients admitted to the intensive care unit. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess the preliminary efficacy of the therapeutic product Alkaline Phosphatase (AP) in severely burned patients admitted to the intensive care unit in reducing the inflammatory response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• partial/full thickness acute thermal burns of at least 15% TBSA • Admission burn ICU • Age ≥18 • Written informed consent from patient or legal representative
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E.4 | Principal exclusion criteria |
• Inclusion in another interventional clinical trial • Patients who are pregnant or lactating • Patients expected to have fatal disease within 24 hours • Patients with chemical burns • Patients who are having an known history of immune system that has been impaired by disease, such as patients with HIV and with a CD4 count of less than 200 cells/mm, neutropenic patients (<0.5 x 109/l) or medical treatment with immunosuppressive effects • Patients who have advanced chronic liver disease confirmed by a Child-Pugh C • Patients with active haematological malignancy
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E.5 End points |
E.5.1 | Primary end point(s) |
The safety as in number of (serious) adverse events within 30 days after initiation of AP treatment is the primary endpoint. Adverse events are defined as any unusual experience occurring to a subject during the study, whether or not considered related to alkaline phosphatase. This includes fever without suspicion, skin rash and signs of an allergic reaction (as suspected by the physician) will be reported. According to Dutch regulations (CCMO) all AE’s and SAE’s will be monitored and reported. To monitor the complications all possible adverse events, expected and unexpected ones, are recorded and noted in the eCRF.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
within 30 days after initiation of the study drug |
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E.5.2 | Secondary end point(s) |
Secondary endpoints will be the daily measured inflammatory markers (e.g. macrophages, neutrophils, lymphocytes, cytokine levels), and daily routine clinical and lab parameters including heart rate, MAP, CPAP/ASB, sepsis/ septic shock criteria, culture proven infection, Hb, PCT, CRP, leucocytes, creatinine, lactate.
Furthermore length of stay ICU/ hospital, time to reach complete (>95%) wound closure, number of surgical procedures, in-hospital mortality and mortality at 30 days.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
until 30 days or discharge from hospital. |
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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 | No |
E.6.4 | Safety | Yes |
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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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.8.5 | 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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When last patients follow-up at 30 days or discharge from hospital. The study will be terminated prematurely if the investigators or safety committee (the independent data monitoring committee) feel that safety of the patients is not guaranteed. The sample size is too small to detect futility of the treatment before all subjects are enrolled. |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | |