E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe traumatic brain injury |
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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 |
This is a small pilot study set to prove the hypothesis that optimisation of abnormal brain tissue pH (correction of brain tissue acidosis) following severe head injury will lead to improvement of cerebral blood flow and metabolism. The latter will be assessed with the use of clinical multimodality monitoring and imaging (cerebral tissiue oxygen, carbon dioxyde and pH sensor, intracranial pressure monitor, transcranial doppler, cerebral microdialysis, PET scan). |
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E.2.2 | Secondary objectives of the trial |
To record clinical outcome of patients, including neuropsychological assessment at 6-9 months after head injury. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
a) patients with head injury requiring ventilation and intracranial pressure monitoring b) abnormal brain tissue pH ( <=7.1) i.e. tissue acidosis as a guide to onset of THAM infusion/pH correction
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E.4 | Principal exclusion criteria |
a) patients <16 years of age b) moribund patients (evidence of significant brain stem injury, fixed dilated pupils, severe extracranial injury etc.). c) deranged coagulation parameters, making monitor insertion hazardous d) renal failure e) liver failure f) rhabdomyolysis or other clinical conditions requiring sodium bicarbonate infusion g) blood pH >7.5 and high plasma osmolarity >340mOsm/L h) pregnancy
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint - change in cerebral monitoring parameters after THAM infusion: brain tissue gases and cerebral oxygenation (pO2, pCO2 and SjO2), brain tissue biochemistry (markers of tissue ischaemia - lactate, pyruvate, lactate/pyruvate ratio and cell damage - glycerol), cerebral blood flow and volume (PET, TCD); ICP, CPP and cerebral autoregulation.
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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 | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
pilot study, patients act as their own controls (i.e. parameters before and after intervention) |
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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 | 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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20 patients will be enrolled in the trial. Data will be analysed after recruitment of the first 10 patients and study will be continued only of appropriate (i. e. more information required). Observation of recognised side effects of THAM affecting patient as well as adverse effects on cerebral metabolism will lead to ending this patient's participation in the trial. The trial will be stopped if the above side effects are observed continuously or in the majority of patients. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |