E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Critically ill patients (SAH, ICB, AVM bleedings, malignant MCA infarcts) under sedation and mechanical ventilation in need of multimodality monitoring, including brain tissue oxygen monitoring and microdialysis. In this population, elevated intracranial pressure (ICP) remains a major complication. As salvage therapy of intractable intracranial hypertension Tromethamine is often administered in an off-label indication for lowering ICP. |
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E.1.1.1 | Medical condition in easily understood language |
Life-threatening intracranial hypertension in patients with severe neurological disease, e.g. intracranial bleeding |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 |
We propose to investigate effects of tromethamine on ICP and regional brain tissue oxygen tension (ptiO2) as measured by Neurovent PTO microprobes in critically ill patients under sedation and mechanical ventilation at a neurosurgical ICU suffering with acute intractable ICP elevation. |
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E.2.2 | Secondary objectives of the trial |
effects of tromethamine 10, 30 and 60 minutes after first bolus administration on: intracranial pressure mean arterial pressure cerebral perfusion pressure cerebral metabolism measured by cerebral microdialysis (glucose, lactate, pyruvate, glycerol, and glutamate) TCD flow velocities arterial blood gas values (pH, pCO2, pO2, bicarbonate, base excess)
dosage and frequency of tromethamine administration concomitant medication for ICP control |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- age > 18 years - patient is in need of multimodality monitoring, including ICP, regional brain tissue oxygen tension (ptiO2) measurement and microdialysis - Clinical indication for THAM administration for treatment of intractable intracranial hypertension (ICP > 20mmHg)
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E.4 | Principal exclusion criteria |
- Patient age < 18 years - blood pH > 7,5 - no need of multimodality monitoring - mannitol administration within the last 3 hours (half-life time of 100min) - immediate need for concomitant administration of mannitol
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E.5 End points |
E.5.1 | Primary end point(s) |
ptiO2 10, 30 and 60 minutes after tromethamine administration |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
10, 30 and 60 minutes after tromethamine administration |
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E.5.2 | Secondary end point(s) |
intracranial pressure mean arterial pressure cerebral perfusion pressure cerebral metabolism measured by cerebral microdialysis (glucose, lactate, pyruvate, glycerol, and glutamate) TCD flow velocities arterial blood gas values (pH, pCO2, pO2, bicarbonate, base excess) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
10, 30 and 60 minutes after tromethamine administration |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
exploratory pharmacodynamic open label single arm study |
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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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
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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LVLS The trial will be terminated prematurely in any of the following cases for example: • Slow recruitment • Poor quality of data • Status of drug development changes • Attempted or proven fraud |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |