Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) in Work up for i.v. Thrombolysis: a Single-centre Study

Background: Stroke remains the third leading cause of death and the first leading cause of handicap in adult age in high-income countries even now when causal revascularisation therapy (intervenous (i.v) thrombolysis and endovascular therapy (EVT) has become generally available. I.v. thrombolysis has been implemented as routine treatment within 4.5 hours of symptom onset based on evidence from randomised controlled trials. Treatment benefit is highly dependent on time from symptom onset to treatment and is therefore strongly related to organisational issues including selection of imaging modality. I.v thrombolysis registration was based on trials using non-contrast Computerized Tomography (CT). In, general however, Magnetic Resonance Imaging (MRI) is considered to imply a higher standard of care. MRI is considered to give more detailed information and improve patient safety. The issue if CT or MRI is 'best' in i.v. thrombolysis work-up has been discussed by stroke scientists for more than a decade, both nationally and internationally. MRI is superior in detecting acute ischaemia and CT is quicker; but the effect of choice of imaging modality on overall efficacy and safety remains to be determined in spite of completion of more than 74.000 i.v. thrombolysis treatments in Europe according to the SITS-MOST registry. Access to primary work up by MRI is frequently regarded as a token of high treatment quality; nevertheless, few centres worldwide are really primarily MRI based. CT is much faster and has no contraindications. This may be crucial as the efficacy of thrombolysis decreases with time to treatment - numbers needed to treat increases with 1 for every 20 minutes, making the question if MRI is only of academic interest a relevant question.

The aim of this study is to determine if choice of primary imaging modality (CT vs MRI) affects efficacy and safety of i.v. thrombolysis in open quasi-randomised design, where imaging allocation was allocated based on the date of admission. The following items will be compared:

1. Radiological exclusion of other causes of symptoms than acute cerebral ischemia
2. Contraindications to scanning method in terms of contrast and magnetism
3. Delay from admission to thrombolytic treatment in minutes
4. Radiological imaging of diagnostic quality
5. Identification of stroke mechanism according to TOAST classification
6. Visual Analogue Scale of patient experience of the admission radiological examination
7. Visual Analogue Scale of the treating physician's experience of decision support prior to prescription of thrombolytic treatment
8. Deviation from radiological Standard Operational Plan
9. Time consumption for radiologists and radiographers in minutes

Method: Patients admitted with acute stroke during office hours and possibly also during daytime in weekends in Bispebjerg University Hospital will be included into the study during a 24 months study period. Based on activity in 2011, the investigators expect a study population of 600 patients. Door to needle time is the parameter/endpoint strongest associated with prognosis and therefore the most relevant from the patient's point of view. This estimate is well within the planned sample size. However, the sample size is extended in order to allow for analysis of less well-defined endpoints including patient experience.

• Study procedures: Patients are evaluated according to usual standard neurological outcome (National Institute of Health Stroke Scale (NIHSS)) performed on admission and on Day 1. Risk factors and co-morbidities are recorded and the stroke mechanism evaluated. The patients or carers are contacted by telephone after approximately 3 months. Recurrence of stroke, Transient Ischemic Attack (TIA), Myocardial Infarction (MI) and cardiac revascularization procedures are registered. If the patient is diseased, time of death and cause of death will be extracted from patient files. The functional outcome is assessed by the modified Rankin Scale (mRS) (including death).
• Patient experience of scan: The patient is asked day 1 about their experience of the scanning procedure by use of visual analogue scales.
• The physicians' certainty of having made the right decision concerning thrombolysis: The doctor notes by using a visual analogue scale (0-10) the strength of the clinical decision to give or not give tissue Plasminogen Activator (tPA) immediately after the bolus, or after the patient is informed that is not indicated.
• Resource use: Time from arrival until treatment initiation are recorded. Potential deviation of resource consumption when derogating from the SOP will be accounted for.
• Data Analysis: Imaging is evaluated during the acute phase. Further, the diagnostic imaging will be systematically and retrospectively evaluated by two senior neuroradiological consultants that are blinded to clinical information except the side of symptoms. X2-test, t-test/Mann-Whitney-test will be used depending on the distribution of the material, as well as uni and multivariate logistic regression analysis. It will be tested if the age, gender and severity affect the results. Data relating to risk factors and co-morbidity will be used to characterize the patient population. Function after 3 months expressed as mRS will be assessed, but the study was not designed to be able to detect an eventual difference in level of functioning after 3 months.