E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Herpes simplex virus type-1 (HSV-1) is the most frequent cause of fatal sporadic encephalitis in humans. Herpes simplex encephalitis (HSE) was one of the first viral infections to be successfully treated with antiviral drugs. Mortality has been significantly reduced since the introduction of acyclovir, a specific inhibitor of HSV replication. Despite appropriate and promptly initiated antiviral therapy the incidence of persistent neurological deficits remain unacceptably high. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
GACHE aims to evaluate the effect on morbidity and mortality of early adjuvant corticosteroids (dexamethasone) in the treatment of adult patients with herpes-simplex-virus-encephalitis.
The major motivation for this trial is the extremely unsatisfactory outcome of patients despite effective antiviral treatment with the actual golden standard Acyclovir.
Primary Endpoint: Binary functional outcome after 6 months measured by the modified Rankin scale (mRS), a seven-point-scale 0 - 6. A mRS-score of 3 to 6 will be seen as an unfavourable outcome.
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints: Mortality after 6 and 12 months, functional outcome after 6 months measured by Glasgow outcome scale (GOS) and quality of life (EuroQol 5D), functional outcome after 12 months (mRS, GOS) and quality of life (EuroQol 5D), neuropsychological testing after 6 months, cranial MRI findings after 6 months, Seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 18 up to and including 85 years
laboratory – proven diagnosis of herpes-simplex-virus-encephalitis (PCR detection of HSV-DNA in the CSF or positive HSV-ASI (>1,5) in the CSF)
focal neurological signs for not more than 5 days
informed consent
women of childbearing potential: negative pregnancy testing in urine |
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E.4 | Principal exclusion criteria |
Systemic treatment with corticosteroids in the last 6 months, however allowed upto 20mg (prednisolone) oral intake Current use of corticosteroids History of hypersensitivity to corticosteroids Two fixed dilated pupils Pre-event score on the modified Rankin Scale > 2 or on the Barthel Index < 95. Pregnancy women of childbearing potential who are not using a highly effective birth control method Breast feeding women Recent history of active tuberculosis or systemic fungal infection Recent history of head trauma or neurosurgery Recent history of peptic ulcer disease Life expectancy < 3 years. Other serious illness that may confound treatment assessment simultaneous participation in another clinical trial previous participation in another clinical trial in the last 30 days previous participation in this clinical trial acute viral infections other than HSVE (herpes zoster, poliomyelitis, chickenpox) HBsAg-positive chronic active hepatitis approx. 8 weeks before to 2 weeks after prophylactic vaccination lymphadenitis following BCG vaccination. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Binary functional outcome after 6 months (measured by the mRS, a seven-point-scale 0-6). A mRS-score of 3 to 6 will be seen as an unfavourable outcome (=failure). |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 35 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 | 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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |