What has Clinical Research in Stroke achieved for Stroke Patients

1
What has Clinical Research in Stroke achieved for
Stroke Patients?

• Gary Ford
• Director, UK Stroke Research Network
• Professor of Pharmacology of Old Age
• Newcastle University
• Consultant Stroke Physician
• Newcastle upon Tyne Hospitals NHS Foundation
  Trust

2
Stroke not for Treatment

• Oxford Textbook of Medicine, 1983
• There is probably little that medical treatment
  can do to alter the immediate prognosis of
  stroke. Both fibrinolytic drugs and
  anti-coagulation increase the risk of
  intracranial bleeding and should usually not be
  used.
• Research advances
• Evidence for Stroke Unit benefits
• Carotid Endarterectomy
• 1997 Aspirin to prevent early recurrent stroke
• 2003 Alteplase licensed for treatment acute
  ischaemic stroke, NICE recommended 2007
• 2006 Hemicraniectomy for malignant MCA infarction

3
Acute Stroke Treatments
Adapted from Gilligan et al 2005
4
The Ischaemic Penumbra
Astrup et al, 1981
5
Outcomes in randomized trials of rt-PA within 3
hours of acute ischaemic stroke
(3 trials, n869)

• Difference/1000 141 extra alive and independent
  (Plt0.01)
• 130 fewer dependent survivors (Plt0.01)
• 12 fewer deaths (NS)
• Cochrane Library

6
Time is Brain

• The typical patient loses 1.9 million neurons
  each minute in which stroke is untreated

Saver, Stroke 2006
7
Stroke Unit Trials
S. AMERICA
JAPAN
Joinville
Osaka
31 clinical trials (6900 patients)
8
Stroke Unit careDeath or Dependency
Stroke unit care better General ward
better
9
Observational studies of stroke unit
implementation
Observational studies of Stroke Unit
Implementation
10
Challenge of Implementation
Stroke Units Thrombolysis

• 1960s First RCT Stroke Unit care
• 1980s First reports thrombolysis
• 1993 Meta-analysis10 RCTs Stroke Unit care
  (n1586)
• 1995 NINDS trial
• 2002 National Audit 1/3 people access
  Stroke Units
• 2004 Meta-analysis thrombolysis 0-3 hr
  trials
• 2006 National Audit 1/3 people 90 Hospitals not
  offering not accessing Stroke Units
  thrombolysis
• 20?? Access for all patients to Stroke Units and
  Thrombolysis

11
Thrombolysis for Myocardial Infarction
12
OXVASC Stroke Risk following TIA
Rothwell et al, Lancet
13
Effect of Carotid Endarterectomy by Time from
Event to RandomisationIpsilateral ischaemic
stroke and operative stroke or death

14
EXPRESS TIA/Minor Stroke

• Early Use of EXisting PREvention Strategies for
  Stroke
• 7 day stroke risk 10
• 5 year before/after study
• Weekly Daily Clinic
• Seen lt 6hr 1.6 26
• Seen lt 24hr 23 54
• Rx at one month
• Statin 63 85
• Clopidogrel Aspirin 8 47
• Also received BP lowering
• Recurrent stroke rate 10 5
• Stroke between seeking 9 0
• medical attention and clinic

Rothwell, Lancet 2007
15
Brain Plasticity

• Neuronal connections and cortical maps are
  remodelled by experience
• Repetitive performance of skilled motor tasks
  increases cortical representation for the muscles
  involved (musicians, Braille readers)
• Long term potentiation. Glutamate plays key role.
• Animal models - late tissue loss around focal
  cortical infarct. Prevented by hand use commenced
  5 days after symptom onset
• Multiple therapeutic approaches
• Physical Therapy
• Stem Cells
• Drug Therapies

16
Tactile Stimulation and Cortical Representation
Johansson Stroke 2000
17
EXCITE Trial Extremity Constraint Induced
Therapy Evaluation
Two weeks constraint induced movement therapy or
usual care in 222 patients 3-9 months after
ischaemic stroke in 7 centres
Wolf, S. L. et al. JAMA 20062962095-2104
18
What has Stroke Research done for Us.

• Stroke units Thrombolysis Carotid
  endarterectomy Carotid stenting
  Aspirin Early supported discharge,
  Hemicraniectomy Constraint rehabilitation
  therapy
• Provided the evidence base for the English Stroke
  Strategy

19
Stroke Rehabilitation Research

• Innovative high quality basic research
• Extensive opportunities with modern imaging to
  develop innovative surrogate markers
• Closer links needed between researchers and
  stroke rehabilitation services that are research
  receptive
• Failure to engender a research culture in
  clinical teams
• Limited patient and carer involvement
• Excellent small studies in single centres
• Multiple therapeutic approaches possible with
  drugs, devices and cognitive interventions
• Need to design and deliver studies that will
  change health care practice- relevant and
  deliverable
• Substantial opportunities to develop effective
  evidence based novel therapies in rehabilitation

20
What does the Stroke Research Network aim to do
for Stroke?

• Develop a world-class health service
  infrastructure for stroke research
• Support and conduct clinical trials and other
  well designed stroke research studies
• Involve people who have had a stroke, their
  carers and the public in stroke research
• Promote collaborative working within the UK
  stroke research community
• Develop an portfolio of stroke research studies
  including prevention, acute care, rehabilitation
  and on-going care
• Work with professional, industry, academic and
  funding bodies to enhance and increase UK stroke
  research

21
Patient Carer and Public Involvement

• PCPI Clinical Study Group strategy and plan
  implemented
• Recruited 15 lay members to other 7 Clinical
  Study Groups
• Attended induction and training all will attend
  UK Stroke Forum
• Contributed to DH consultations research bids
  research workshops speakers at conferences
• 37 lay members in LRNs supported by network leads
  and managers

22
Adopted Studies

• 42 studies within the SRN study portfolio
• 3 commercial and 39 non-commercial sponsors
• 5 in set-up 5 closed/in follow-up
• Active portfolio increased Open studies Apr
  2006 18 Nov 2007 32
• Research strands
• 9 acute studies
• 13 prevention studies
• 3 primary care studies
• 14 rehabilitation studies
• 1 joint acute / rehabilitation study
• 1 joint primary care / rehabilitation study
• 1 joint prevention / primary care study

23
SRN Accrual
UK Accrual has doubled first 7 months 1017
2114 patients
24
SRN Study Accrual
25
SRN Accrual by Research Strand
26
SRN Accrual by Research Sponsor
27
What have the Romans done for us.

• Sanitation, Medicine, Education, Wine, Public
  order, Irrigation, Roads, a fresh water system,
  Public health

28
What has SRN done for Stroke?

• Develop a world-class health service
  ? infrastructure for stroke research
• Support and conduct clinical trials and
  ? other well designed stroke research studies
• Involve people who have had a stroke, their ?
  carers and the public in stroke research
• Promote collaborative working within the UK ?
  stroke research community
• Develop a portfolio of stroke research
  studies including prevention, acute,
  rehabilitation and on-going care ongoing
• Work with professional, industry,
  academic and funding bodies to enhance and
  increase UK stroke research ongoing