E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
severely injured trauma patients with lactic acidosis due to hemorrhagic shock |
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E.1.1.1 | Medical condition in easily understood language |
severely injured trauma patients with lactic acidosis due to hemorrhagic shock |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023676 |
E.1.2 | Term | Lactic acidosis |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050841 |
E.1.2 | Term | Hemorrhagic shock |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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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 primary objective is to evaluate the safety and efficacy of 250 mL MP4OX treatment compared to 250 mL of normal saline solution plus replacement doses if continued hemorrhage, in addition to standard treatment, in severely injured trauma patients with lactic acidosis due to hemorrhagic shock. |
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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)Informed consent obtained before any study-related activities (study-related activities are any procedure that would not have been performed as standard of care for the patient)
2)Trauma injury (blunt and/or penetrating) resulting in lactic acidosis due to hemorrhagic shock
3)Acidosis (blood lactate level ≥ 5 mmol/L; equivalent to 45 mg/dL) arterial or venous |
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E.4 | Principal exclusion criteria |
1)Massive injury incompatible with life
2)Normalization of lactate prior to dosing (≤ 2.2mmol/L)
3)Patients with evidence of severe traumatic brain injury as defined by ANY one of the following:
a)Known non-survivable head injury or open brain injury
b)Glasgow Coma Score (GCS) = 3, 4 or 5
c)Known AIS (head region) ≥ 4 shown by an appropriate imaging methodology
d)Contemplated CNS surgery
e)Abnormal physical exam indicative of severe CNS or any spinal cord injury above T5 level
NOTE: Patients with a GCS of less than 6 at the time of enrollment may be enrolled, but it is expected that if they are enrolled, they will clearly meet all of the following conditions:
- Documented GCS of 6 or greater at the scene.
- No physical evidence of head injury at the scene
- No evidence of brain injury by appropriate imaging techniques at the hospital
- The patient is intubated and sedated and the depressed GCS can be reasonably be attributed to the sedation given to perform or maintain intubation
- No other exclusionary neurological conditions (such as high spinal cord injury etc).
4)Cardiac arrest prior to randomization
5)Age below the legal age for consenting
6)Estimated time from injury to randomization> 4 hours
7)Estimated time from hospital admission to randomization > 2 hours
8)Known pregnancy
9)Use of any oxygen carrier other than RBCs
10)Known previous participation in this study
11)Professional or ancillary personnel involved with this study
12)Known receipt of any investigational drug(s) within 30 days prior to study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of patients discharged from hospital through day 28 and alive at the Day 28 Follow up visit. |
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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) |
• Hospital-free days (over 28 days)
• ICU-free days (over 28 days)
• Ventilator-free days (over 28 days)
• CTCOFR14 (evaluated at 14 days)
• CTCOFR21 (evaluated at 21 days)
• Lactate clearance assessed by:
�� Proportion of patients who normalize (≤ 2.2 mmol/L) lactate levels by
2, 4, 6, 8 and 12 hours
�� 2-hour lactate clearance (Hour 0 to Hour 2), which will be calculated as follows:
(Lactate0-hour– Lactate 2-hour) / (Lactate 0-hour) X 100
• Proportion of patients remaining in hospital through Day 28
• Proportion of patients remaining in ICU through Day 28
• Proportion of patients remaining on ventilator through Day 28
• Number of days in hospital
• Number of days in ICU
• Number of days on the ventilator
• Duration of ICU stay for survivors (evaluated at Day 28)
• All-cause 48-hours mortality
• All-cause 28-days mortality
• Time (days) from randomization to death
• Time (days) from randomization to discharge from hospital
• Time (days) from randomization to ICU discharge
• Time (days) from randomization to liberation from mechanical ventilation
• Daily SOFA score
• Daily modified Denver score |
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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) | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Colombia |
France |
Germany |
Israel |
New Zealand |
Norway |
Singapore |
South Africa |
Spain |
Switzerland |
United Kingdom |
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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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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 | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |