Penumbra and Recanalisation Acute Computed Tomography in Ischaemic Stroke Evaluation

Study Overview
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Brief Summary
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Stroke affects over 125,000 people each year in the UK and leaves at least 50% disabled. Treatment of stroke caused by a blockage in a blood vessel (ischaemic stroke), with clotbusting drugs improves the chances of good recovery, but must be given within 4.5 hours of onset. Currently only a small proportion of patients who arrive in hospital within 4.5 hours are treated. This is largely due to uncertainty about diagnosis and concerns about risk of bleeding associated with clotbusting medication. Patients with mild or improving symptoms in particular are often not treated because of uncertainty about relative risks and benefits. However, around one third of these patients go on to be significantly disabled. Routine CT scanning often does not show abnormalities in acute stroke (which take hours to become easily visible), and cannot show the extent or severity of blood flow changes in ischemic stroke. We wish to investigate the value of additional CT scanning that gives information on the blood vessels (angiography, CTA) and blood flow to the brain (perfusion, CTP) by undertaking a randomised trial. Extra scans are done in the same scanner and involve some extra radiation, injections of a contrast dye, and some extra time to acquire process and interpret. The extra scans may allow better treatment decisions for patients by increasing diagnostic certainty and by better assessment of stroke severity. However, we do not know whether the potential gains from better selection justify the resources and potential treatment delays that are involved. We will investigate whether the proportion of patients given clotbusting drugs differs between the two scanning protocols; and whether the outcomes differ, using standard measures of disability. We will also investigate whether use of different scanner manufacturers' software affect interpretation of scans.

Official Title
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Penumbra and Recanalisation Acute Computed Tomography in Ischaemic Stroke Evaluation

Conditions
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Ischaemic Stroke

Intervention / Treatment
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* Other: control imaging
* Other: additional multimodal imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of stroke eligible for IV rtPA according to current guidelines Informed consent Male or nonpregnant female ≥18 years of age Within 4.5 hours of onset as defined by time since last known well Exclusion Criteria: Contraindications to thrombolytic drug treatment for stroke Pregnancy Known impaired renal function precluding contrast CT Known allergy to CT contrast agents Severe concurrent medical condition that would prevent participation in study procedures (e.g. cardiac failure with severe pulmonary oedema) or with life expectancy ≤ 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control imaging (NCCT)<br>Standard imaging | Other: control imaging<br> <br> |
| Experimental: additional multimodal imaging<br>CT + CTA + CTP | Other: additional multimodal imaging<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients receiving Intravenous Recombinant Tissue Plasminogen Activator (IV rtPA) | Data will be collected at 4.5 hours from onset, comparison of proportion of patients receiving treatment will only be assessed at the end of the study | 4.5 hours from onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment decision and administration |  | 4.5 hours from onset | 
| 3 month modified Rankin Scale (mRS), by intention to treat, using a Cochran Mantel Haeszel distribution analysis |  | 90 days from onset | 
| Safety - symptomatic Intracerebral hemorrhage (ICH) and major infarct swelling rates |  | 7 days from onset | 
| Diagnostic sensitivity and specificity | Data will be collected at 4.5 hours from onset, comparison of proportion of patients receiving treatment will only be assessed at the end of the study | 4.5 hours from onset | 
| 3 month mRS distribution in patients i) selected for IV rtPA and excluded from IV rtPA |  | 90 days from onset | 
| Comparisons of efficacy & safety outcomes in Target Population (imaged as per randomised allocation and per protocol) | Data will for safety will be collected at day 7, data for efficacy will be collected at day 90. Comparison between to groups will be done at the end of the study | 90 days after onset | 
| Interobserver Agreement for rtPA eligibility between local and centrally processed CTP/CTA | Scans will be collected, centrally processed and presented again to the local clinicians in electronic form. Participants will be asked about clinical decision in view of centrally processed scans. The final data about inter observer agreement will be available at the end of the study | Six months after recruitment | 
| Interobserver agreement in interpretation of locally processed Computed Tomography Perfusion (CTP) scans | Scans will be collected, centrally processed and presented again to the clinicians in electronic form. The final data about inter observer agreement will be available at the end of the study | Six months after recruitment |