E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic subdural haematoma |
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E.1.1.1 | Medical condition in easily understood language |
bleed on the surface of the brain |
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E.1.1.2 | Therapeutic area | Body processes [G] - Biological Phenomena [G16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042361 |
E.1.2 | Term | Subdural haematoma |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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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 |
To investigate whether a two-week course of dexamethasone can improve the 6 month functional outcome of patients with symptomatic chronic Subdural Haematoma (CSDH) by reducing the rate of surgical intervention and the recurrence rate. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: -Number of CSDH- related surgical interventions undertaken during the index admission -Number of CSDH-related surgical interventions undertaken during subsequent admissions in the follow-up period. -Outcome questionnaires to assess quality of life and health at 3 and 6 months -Length of stay in neurosurgical unit. -Discharge destination from neurosurgical unit -Length of stay in secondary care (local hospital). -Health-economic analysis. -Adverse events. -Assess the biological action of dexamethasone within CSDH fluid. -Assess the role of dexamethasone in cerebral perfusion (blood flow) and oedema (swelling) in CSDH. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Exploratory outcome measures sub-study, 01 Mar 2016, Version 2.0 - This sub-study has been set up to help understand how dexamethasone is working to improve outcome in CSDH. We aim to assess the biochemistry of the CSDH fluid to look at how dexamethasone alters the inflammatory profile of the fluid to reduce recurrence. We will also be using transcranial doppler (a non-invasive USS) and MRI to assess how dexamethasone changes the cerebral blood flow (perfusion) and swelling (oedema) to help neurological recovery from CSDH. |
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E.3 | Principal inclusion criteria |
1.Adult patients (aged 18 years or older) 2.Symptomatic CSDH confirmed on cranial imaging (predominantly hypodense or isodense crescentic collection along the cerebral convexity on CT). 3.Informed consent or IHP authorisation
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E.4 | Principal exclusion criteria |
1.Patients with conditions where steroids are clearly contra-indicated 2.Patients who are already on (or within 1 month) regular oral or intravenous steroids 3.Previous enrolment in this trial for a prior episode. 4.Patients in whom the time interval from admission to neurosurgical unit to initiation of trial drug exceeds 72 hours. 5. CSDH in the presence of a cerebrospinal fluid (CSF) shunt. 6. Lactose intolerance or any known hypersensitivity to dexamethasone or any of the IMP (investigational medicinal product) excipients 7. Patients with a history of psychotic disorders 8. Concurrent enrolment in any other trial of an investigational medicinal product 9. Previous cranial neurosurgery (sub-study only) 10. Active malignancy(sub-study only) 11. Currently receiving immunosuppressive drug therapy (sub-study only) 12. Renal dysfunction (MRI sub-study only) 13. Pacemaker or metal implants (MRI sub-study only) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The clinical outcome, as measured by the Modified Rankin Scale (mRS) at 6 months |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months post randomisation |
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E.5.2 | Secondary end point(s) |
1.Number of CSDH-related surgical interventions undertaken during the index admission. 2.Number of CSDH-related surgical interventions undertaken during subsequent admissions 3.Glasgow Coma Scale (GCS) 4.mRS score 5.Barthel Index 6.Mortality 7.EuroQOL (EQ-5D) 8.Length of stay in hospital. 9.Discharge destination from NSU. 10.Length of stay in rehabilitation. 11.Health-economic analysis. 12.Adverse events. 13.Assessment of inflammatory mediators in CSDH fluid and blood. 14.Cerebral perfusion measured on MRI and TCD. 15.Cerebral swelling measure on MRI. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessment of 1-9 and 12 at discharge form Neurosurgical unit Assessment of 6 and 12 at day 15 and day 30 Assessment of 2,4,5,7 at 3 months Assessment of 2,3,5,6,7 and 11 at 6 months Assessment of 13 at time of surgery (if performed) and up to 48hrs post-operatively. Assessment of 14 and 15 within 72hrs of admission, repeated within 14 days of admission and at 6-12 weeks. |
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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.6.13.1 | Other scope of the trial description |
Improve the 6mth functional outcome, reduce the rate of surgical intervention and recurrence rate |
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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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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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6 months after the LVLS (when the last 6 months follow-up questionnaire will be received) |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 1 |