E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Trauma with lactic acidosis due to hemorrhagic shock |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023676 |
E.1.2 | Term | Lactic acidosis |
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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 MP4OX treatment compared to Ringer’s Lactate solution, in addition to standard of care, in severely injured trauma patients with lactic acidosis due to hemorrhagic shock. |
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E.2.2 | Secondary objectives of the trial |
The following secondary efficacy variables will be measured for each patient during the study:
• All-cause 28 day mortality
• Time (days) from randomization to death
• Ventilator-free days (over 28 days)
• Time (days) from randomization to ventilator-free days
• ICU-free days (over 28 days)
• Time (days) from randomization to ICU free days
• Daily SOFA score
• Daily modified Denver score
• CTCOFR21 (evaluated at 21 days)
• CTCOFR14 (evaluated at 14 days)
• Hospital-free days (over 28 days)
• Time (days) from randomization to hospital free days |
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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. Adult male or female (surgically sterile or post-menopausal or not pregnant), aged 18 to 80 years or of legal age to consent for participation in an investigational drug trial as per local law.
3. Trauma injury (blunt and/or penetrating) resulting in lactic acidosis due to hemorrhagic shock. a. Lactic acidosis (lactate ≥ 5 mmol/L; equivalent to ≥ 45 mg/dL) |
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E.4 | Principal exclusion criteria |
1. Not expected to survive 24 hours after randomization (based on physician judgment) a. Massive injury incompatible with life
2. 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; Glasgow Coma Score (GCS) = 3, 4 or 5, or known AIS = 5 if GSC > 5 b. Immediate open intracranial operation c. Abnormal physical exam indicative of severe CNS or spinal injury
3. Patients with significant ongoing uncontrolled hemorrhage where control of bleeding is not expected within 2 hours of randomization.
4. Cardiac arrest prior to dosing.
5. Estimated time from injury to dosing > 4 hours.
6. Estimated time from hospital admission to randomization > 2 hours.
7. Known or suspected pregnancy (confirmed by urine test).
8. Previous participation in this study.
9. Professional or ancillary personnel involved with this study.
10. 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 2-hour lactate clearance.
Lactate clearance will be calculated as follows: (Lactate 0-hour– Lactate 2-hour) / (Lactate 0-hour) X 100
Patients who do not complete the infusion of investigational product nor have both hour zero and 2-hour lactate samples collected will be replaced.
The period of maximum lactate clearance (%) will also be calculated.
The minimum effective dose for MP4 group will be chosen to maximize the decrease in lactate levels within the first 8 hours after completion of investigational product infusion. |
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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 | 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 | 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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | Information not present in EudraCT |
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 |
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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
| |
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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |