E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042244 |
E.1.2 | Term | Stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
Does treatment with erythropoetin (EPO) during post acute rehabilitation of non-thrombolysed patients improve functional recovery in stroke patients?
Can multimodal MR imaging be used for in vivo monitoring of brain repair in humans and do MRI parameters correlate with clinical measures of function recovery. |
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E.2.2 | Secondary objectives of the trial |
Does treatment with EPO result in functional/structural restoration in the peri-infarct area that can be visualised using MRI techniques?
What is the optimal timing of administration of EPO therapy to be effective?
Is EPO treatment safe in non-thrombolysed stroke patients undergoing rehabilitation?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 18-85 years, male and females
Supratentorial ischaemic stroke, confirmed on imaging.
Recruited within 48 hours of stroke onset. Time of onset is when symptoms began; for stroke that occurred during sleep, time of onset is when patient was last seen or was self-reported to be normal.
Motor impairment of MRC grade <=4 affecting the upper or lower limb
Reasonable expectation of availability to receive the full course of therapy, and to be available for subsequent follow-up visits.
Reasonable expectation that patient will receive standard post-stroke physical, occupational and speech therapy as indicated.
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E.4 | Principal exclusion criteria |
• Pre-stroke modified Rankin Score (mRS) >2
• Thrombolytic treatment with tPA following the index stroke.
• Patients presenting with hemorrhagic and/or brain stem stroke.
• Contraindications to MRI
• Women who may be pregnant or breast-feeding.
• Serum hemoglobin > 16 g/dL (males) or > 14 g/dL (females); or platelet count > 400,000/mm3.
• Advanced liver, kidney, cardiac or pulmonary disease (serum bilirubin > 1.5 x upper limit of normal (ULN), Alkaline phosphatase > 2.5 x ULN, GGT>2.5xULN).
• Serum creatinine >200 micromol/l
• History of clotting disorders.
• Expected survival < 1 year.
• Hypersensitivity or other contraindication to erythropoeitin or to any of the excipients as per SPMC.
• A known diagnosis of epilepsy
• A known diagnosis of cancer (except non-malignant skin cancer).
• Uncontrolled hypertension (BP persistently > 220 mm Hg systolic or 120 mm Hg diastolic despite antihypertensive therapy).
• Pre-existing and active major psychiatric or other chronic neurological disease.
• Currently participating in another investigational study.
• Cognitive or communication problems that limit ability to provide informed consent or follow assessment procedures
• Lack of capacity as defined by the Mental Capacity Act to provide informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
Fugl-Meyer scale score (Primary outcome measure)at 90 days |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 90 days after the onset of Stroke |
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E.5.2 | Secondary end point(s) |
Measured at 30 and 90 days
– NIHSS score
– NIHSS score change from baseline
– Fugl-Meyer scale score change from baseline
– 10 metre timed walk test
– Functional Independence Measure
– Stroke Impact Scale
– Modified Rankin Scale
– Mortality
Measured at 90 days:
– FLAIR measurement of infarct volume
– Diffusion Tensor Imaging Tractography of white matter tracts
– Arterial Spin Labelling measurement of regional perfusion
– Spectroscopy for N-acetylaspartate (NAA), Myoinositol, Choline and other stroke related metabolites
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 30 and 90 days after the onset of Stroke |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Routine care/no intervention |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 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 | 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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At 3 months of follow up when all subjects have been recruited. No interim analyses are planned. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |