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The monitoring study is an academia-driven attempt to get a European database on the results of patients treated with rt-PA in everyday practice. The Steering Committee is listed on this slide. SITS-MOST is supported by an unrestricted grant from Boehringer Ingelheim GmbH.
Safe Implementation of Thrombolysis in Stroke SITS Collaboration
Nils Gunnar Wahlgren, Antoni Davalos, Martin Grond, Cesare Fieschi, Werner Hacke,
Markku Kaste, Rüdiger von Kummer, Vincent Larrue, Kennedy R Lees, Joanna Wardlaw for the
SITS collaborators
ECASS 3 vs. SITS-MOST
The Third
European Cooperative Acute Stroke Study
- ECASS 3 -
and
The Safe Introduction of Thrombolysis in Stroke-Monitoring Study
- SITS-MOST -
What Is SITS International Stroke Thrombolysis Register (SITS-ISTR)?
SITS-ISTR is:
- an internet-based, on-line data entry, immediate feed back reporting, ongoing audit of thrombolysis in acute stroke
- It has national coordinators in almost all EU countries and beyond
- It is running; around 5000 patients over 5 years included (3260 in SITS MOST)
- Largest database for acute stroke treatment worldwide
What Is SITS-MOST?
SITS-MOST is:
- Is a study built on the SITS-ISTR
- Aims to include > 1000 patients treated < 3 hours
- Defines inclusion criteria
- Includes qualified centres, with or without experience from thrombolysis in stroke
- Wants to evaluate whether routine use of intravenous rt-PA within 3 hours after onset of stroke symptoms is at least as safe and as beneficial as in the randomised controlled trials
Intravenous thrombolytic therapy with alteplase (rt-PA) is an evidence-based treatment for acute ischaemic stroke. Successful treatment induces reperfusion by dissolving blood clots. Reperfusion interrupts ischaemic pathophysiology, reducing the evolution of stroke and limiting neurological deficit, disability and the secondary complications of stroke. However, there is a substantial risk of haemorrhagic complications.
EMEA’s Committee for Proprietary Medicinal Products (CPMP) has now conditionally approved alteplase (Actilyse®) for use in selected patients with acute ischaemic stroke.
In order to achieve the benefits demonstrated in clinical trials, while limiting the observed potential for haemorrhagic complications, continuous quality control through clinical audit is needed as routine clinical use of alteplase in stroke becomes established. SITS-ISTR is a clinician-driven international monitoring registry for auditing the safety and efficacy of routine therapeutic use of thrombolysis in acute ischaemic stroke, through which SITS-MOST will be performed.
The aim of SITS-MOST is to verify that intravenous thrombolysis treatment is as safe and efficacious in routine clinical practice in centres with appropriate facilities as it has been shown to be in randomised controlled trials. It also aims to provide immediately upgraded statistical reports to show how a centre’s outcome compares to other centres. This should lead to improved efficacy and safety over time.
References:
SITS-MOST, www.acutestroke.org
Wahlgren NG. Cerebrovasc Dis 2005; 19 (Suppl 2): 156.
PRIMARY
- Symptomatic intracranial haemorrhage (SICH)/ Parenchymatous haemorrhage (PH2)
- - Intracerebral haemorrhage (parenchymatous
haemorrhage type 2), at the 22-36 hours post-treatment
scan, combined with neurological deterioration leading
to an increase of 4 points on the NIHSS
- Death
SECONDARY
- Independence (mRS 0-2) compared with expected outcome in a prognostic model based on the placebo arm of randomized controlled trials
- Therefore, the main observational variables in SITS-MOST will include symptomatic intracranial haemorrhage, parenchymal haemorrhage, death and independence (modified rankin
scale 0-2).
Reference:
SITS-MOST, www.acutestroke.org
Wahlgren NG. ESC Bologna 2005. Oral presentation.
A systematic review was given by proportions of SICH, death and independence per 100 patients and 95% confidence intervals (CI) in randomised controlled trials mentioned as shown in this table.
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Proportions of SICH, death and independence per 100 patients and 95 % confidence intervals (CI) in randomized controlled trials |
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SICH
(N = 465) |
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Death
(N = 479) |
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Independence
(N = 465) |
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| Proportion |
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95% CI |
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Proportion |
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95% CI |
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Proportion |
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95% CI |
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6.1-11.1 |
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17.3 |
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13.9-20.7 |
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50.1 |
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45.6-54.6 |
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Reference:
SITS-MOST, www.acutestroke.org
Wahlgren NG. ESC Bologna 2005. Oral presentation.
There will be independent follow-up of haemorrhage, evaluated by the Brain Imaging Committee. Mortality and independence will be reported at 3 months by the participating centres.
- Haemorrhage – evaluated by Brain Imaging Committee: von Kummer + Wardlaw, coordinated by Hårdemark
- Mortality, independence – follow up by National Coordinating centre in each country
- Compliance – site monitoring etc by national co-ordinator assisted by CRA staff from BI
Reference:
SITS-MOST, www.acutestroke.org
Wahlgren NG. ESC Bologna 2005. Oral presentation.
The number of recruited patients is ever increasing. On this graph 3095 patients included until April 2005 are depicted. The last number was 3260 patients as per May 24th 2005 in 253 centres.
Reference:
Wahlgren NG. Cerebrovasc Dis 2005; 19 (Suppl 2): 156.
SITS-MOST has now been running for nearly two years with clinical outcome in line with RCT results
The main outcome results of SITS-MOST so far, mortality, independence rate at 3 months and rate of SICH, are all broadly in line with the RCTs. The overall mortality rate is slightly lower than that in the RCTs. Mortality rates seem to be lower at the more experienced centres, and the causes of this are being investigated. The independence rate is slightly better in SITS-MOST (51%) than in the RCTs (50.1%), and the SICH rate is slightly lower than that in the RCTs. Overall the results are reassuring and encouraging.
Reference:
SITS-MOST, www.acutestroke.org
Wahlgren NG. ESC Bologna 2005. Oral presentation.
* Experienced centre: Participated in ECASS 1/II or treated at least 5 patients before joining SITS.
** New centre: No such experience.
SITS-MOST allows centres to compare their characteristics with those of other centres, and there are dramatic differences. Median door-to-imaging times for centres vary from 9 minutes (best practice) to 90 minutes (worst practice), with a median of 28 minutes for all centres. Median door-to-needle times range from 20 minutes to 139 minutes with the median for all centres of 73 minutes.
Reference:
SITS-MOST, www.acutestroke.org
Wahlgren NG. ESC Bologna 2005. Oral presentation.
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Trial Period |
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Baseline |
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Treat-
ment
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Post-
treat-
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Follow-up |
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Visit No: |
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1A |
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1B |
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1C |
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2 |
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3 |
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4 |
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Day of visit: |
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1 |
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1 |
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1 |
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2
(24 h Post treat-ment) |
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7
(or stroke unit dis-charg) |
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9
(Final follow up) |
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Informed consent |
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x |
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In-, exclusion criteria |
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x |
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Demographics |
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x |
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Medical history |
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x |
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Concomitant diagnoses |
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x |
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Previous treatment |
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CT/MR |
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x |
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x* |
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(x**) |
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NIHSS |
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x |
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x |
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x |
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x |
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Blood pressure |
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x |
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x |
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x |
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x |
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Treatment delay |
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x |
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rt-PA administration |
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x |
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Concomitant treatment |
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x |
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x |
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x |
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x |
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mRS |
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*with a time window of 22-36 hours
**Optional, only needed in case of clinical deterioration
As with SITS-ISTR, centres enter their data in the register over the internet by responding to
specified questions. The data focus on:
- Time delays in management
- Baseline and demographic data
- Baseline stroke severity (NIH score)
- Baseline imaging studies
- Follow-up NIH score and imaging
Results evaluation – modified rankin score at 3 months together with details of any complications such as
haemorrhages.
Reference:
SITS-MOST, www.acutestroke.org
Wahlgren NG. ESC Bologna 2005. Oral presentation. |
