Percutaneous vascular interventions versus intravenous

thrombolytic treatment for acute ischaemic stroke (Protocol)

Bruins Slot KMH, Berge E, O’Rourke K, Wardlaw JM

This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane
Library 2011, Issue 9
http://www.thecochranelibrary.com

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol) i
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Protocol]

Percutaneous vascular interventions versus intravenous

thrombolytic treatment for acute ischaemic stroke

Karsten MH Bruins Slot1 , Eivind Berge2 , Killian O’Rourke3 , Joanna M Wardlaw4

1 Department of Internal Medicine, Oslo University Hospital Ullevål, Oslo, Norway. 2 Department of Cardiology, Oslo University
Hospital Ullevål, Oslo, Norway. 3 Dublin Neurological Institute, Mater University Hospital, Dublin 7, Ireland. 4 Division of Clinical
Neurosciences, University of Edinburgh, Edinburgh, UK

Contact address: Karsten MH Bruins Slot, Department of Internal Medicine, Oslo University Hospital Ullevål, Oslo, NO-0407,
Norway. kbruinsslot@yahoo.no.

Editorial group: Cochrane Stroke Group.

Publication status and date: New, published in Issue 9, 2011.

Citation: Bruins Slot KMH, Berge E, O’Rourke K, Wardlaw JM. Percutaneous vascular interventions versus intravenous throm-
bolytic treatment for acute ischaemic stroke. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD009292. DOI:
10.1002/14651858.CD009292.

Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT
This is the protocol for a review and there is no abstract. The objectives are as follows:
The objective of this review is to assess the safety and effectiveness of percutaneous vascular interventions compared with intravenous
thrombolytic treatment for acute ischaemic stroke.

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol) 1
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
BACKGROUND
Most ischaemic strokes are caused by the blockage of a cerebral
artery by a thrombus. Thrombolytic treatment with pharmaco-
logical agents aims to dissolve the thrombus in the cerebral artery,
leading to recanalisation and restoration of distal cerebral blood
flow and an improved functional outcome.
Prompt intravenous administration of recombinant tissue plas-
minogen activator (rtPA) is an effective treatment for selected pa-
tients with acute ischaemic stroke and is currently the treatment
of choice for acute ischaemic stroke within three to 4.5 hours after
stroke onset (Adams 2007; Del Zoppo 2009; ESO 2009; Wardlaw
2009). Other intravenously administered thrombolytics (for ex-
ample desmoteplase) are currently under evaluation for use in pa-
tients with acute ischaemic stroke.
Thrombolytic agents can also be administered directly at the site
of the occluded cerebral artery. There is evidence that intra-ar-
terial thrombolytic treatment with urokinase could be beneficial
in ischaemic stroke patients with proximal middle cerebral artery
occlusions (Ogawa 2007). Intra-arterial thrombolysis with rtPA,
however, is not substantiated by any randomised controlled tri-
als (RCTs) but observational data and non-randomised compar-
isons are available and might indicate improved recanalisation rates
compared with intravenous thrombolytic treatment (Mattle 2008;
Nedeltchev 2006).
Recanalisation can also be achieved by percutaneous vascular in-
terventions using a mechanical device to retrieve or disrupt the
thrombus. Several of these devices are currently being used, or
studied, for treating ischaemic stroke patients (Nogueira 2009).
The devices can roughly be divided into five different categories
according to their mechanism of action. Thrombectomy devices
are suction or ’grasper’ devices that aim to retrieve a thrombus by
applying force on the proximal base or basket or snare-like devices
that apply force on the distal base; thrombus disruption devices
use a guide wire or snare to mechanically fragment a thrombus;
thromboaspiration devices use a microcatheter or guiding catheter
to aspirate the thrombus; sonothrombolysis devices use ultrasonic
vibrations to dissolve a thrombus; and stent devices which aim to
restore cerebral blood flow by entrapping the thrombus between
the stent and the blood vessel.
Description of the condition
Ischaemic stroke is one of the major causes of death and disability
worldwide (Strong 2007). Stroke demands a substantial personal
and financial burden on society, which most likely will increase
during the coming decades as a result of the ageing populations in
most developed countries (Rosamund 2008; Strong 2007).
Why it is important to do this review
Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Percutaneous vascular interventions may be used as primary or ad-
junctive treatment strategies in acute ischaemic stroke and could
have several potential advantages over pharmacological throm-
bolytics. First, these interventions may lessen and even preclude
the use of pharmacological thrombolytic agents, thereby reducing
the risk of (intracranial) haemorrhages that are associated with the
latter. Second, they could extend the treatment window for acute
ischaemic stroke beyond the current three to 4.5 hours with intra-
venous rtPA treatment. Third, percutaneous interventions could
be used in patients who have contraindications to pharmacological
agents (for example abnormal haemostasis or recent surgery). Fi-
nally, such interventions could provide faster recanalisation com-
pared with pharmacological thrombolysis and further minimise
ischaemic cerebral damage (Nogueira 2009).
On the other hand, there are several potential disadvantages of
percutaneous vascular interventions in treating acute ischaemic
stroke. These might pertain to the technical difficulties of navigat-
ing the percutaneous device into the intracranial circulation, the
need for centres with proper equipment and expertise, complica-
tions related to trauma to the vasculature (for example dissection,
perforation or rupture), and fragmentation of the thrombus caus-
ing occlusion in distal cerebral blood vessels.
The use of percutaneous endovascular interventions for achiev-
ing recanalisation has become more widespread in recent years
(Nogueira 2009). Still, it remains unclear whether these interven-
tions are more effective and safer than intravenous thrombolytic
treatment, and which patients could benefit the most. A direct
comparison of these two treatments might help clinicians in se-
lecting the best treatment option for patients with acute ischaemic
stroke. We therefore aim to perform a systematic review of all
RCTs that directly compare percutaneous vascular interventions
with intravenous thrombolytic treatment.
OBJECTIVES
The objective of this review is to assess the safety and effectiveness
of percutaneous vascular interventions compared with intravenous
thrombolytic treatment for acute ischaemic stroke.
METHODS
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) that directly compare a per-
cutaneous vascular intervention with intravenous thrombolytic
treatment in patients with acute ischaemic stroke.
2
Types of participants
Patients with a definite ischaemic stroke confirmed by either a
computerised tomography (CT) or magnetic resonance imaging
(MRI) scan, who are eligible for treatment with an intravenous
thrombolytic agent or a percutaneous vascular intervention, or
both.
Types of interventions
All percutaneous arterial endovascular techniques aimed at revas-
cularisation in acute ischaemic stroke, including but not confined
to:
• endovascular thrombectomy (retriever devices);
• thromboaspiration;
• mechanical fragmentation of the thrombus;
• implantation of stents;
• intra-arterial sonothrombolysis.
The comparison therapy will be intravenous thrombolytic treat-
ment. We will include all RCTs that studied thrombolytic agents
(irrespective of administered dose or type of agent) compared with
a percutaneous vascular intervention.
The comparison between intra-arterial and intravenous throm-
bolytic treatment is the scope of another review (Mielke 2009) and
trials of intra-arterial thrombolytic treatment alone should not be
included in the present review. Intra-arterial agents can, however,
be given as an adjunct to other percutaneous vascular interven-
tions.
Types of outcome measures
Primary outcomes
Functional outcome at the end of the scheduled follow-up period,
categorised by the modified Rankin score (mRS): 0 to 2 (indepen-
dence), 3 to 6 (dependency and death).
Given that some trialists prefer a definition of ’favourable out-
come’, defined as mRS score 0 to 1 only, we will also seek data
on the number of patients in each individual modified Rankin
category. If the modified Rankin score is not reported, we will use
the trial’s definition of functional outcome.
Secondary outcomes
1. Deaths from all causes, both: (a) during the first two weeks,
and (b) at the end of the scheduled follow-up period.
2. Symptomatic intracranial haemorrhage (sICH) within the
first two weeks and at the end of the follow-up period. sICH will
be defined according to the criteria that were used in the third
European Cooperative Acute Stroke Study (ECASS III) (Hacke
2008). When sICHs are not reported according to these criteria,
we will consider using the trial’s definition.
Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
3. Assessment of revascularisation or recanalisation according
to the Cerebral Infarction Perfusion Categories (Higashida 2003)
and Thrombolysis In Myocardial Infarction (TIMI) reperfusion
score (Khatri 2005).
Search methods for identification of studies
See the ’Specialized register’ section in the Cochrane Stroke Group
module.
Electronic searches
We will search the trials registers of the Cochrane Stroke Group and
the Cochrane Peripheral Vascular Diseases Group. In addition, we
will search the following electronic databases and trials registers:
• Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library, latest issue);
• MEDLINE (from 1950) (Appendix 1);
• EMBASE (from 1980);
• Stroke Trials Directory (www.strokecenter.org/trials);
• ClinicalTrials.gov (www.clinicaltrials.gov);
• Current Controlled Trials (www.controlled-trials.com).
We will modify the MEDLINE search strategy (Appendix 1) for
the other databases.
Searching other resources
In an effort to identify further published, unpublished, ongoing,
and planned trials we will:
• screen reference lists of relevant trials;
• contact manufacturers of relevant interventional
radiological equipment;
• contact authors, colleagues, and researchers active in the
field;
• identify and handsearch the proceedings of relevant
conferences;
• search Google Scholar;
• use the Science Citation Index Cited Reference search for
forward tracking of relevant references.
No language restrictions will apply to our searches, and we will
attempt to obtain translations of potentially relevant non-English
language papers.
Data collection and analysis
Selection of studies
Three review authors (KBS, KOR and EB) will independently
screen titles and abstracts of references identified by the searches.
We will obtain full paper copies of those trial reports which, from
3
the title and abstract, appear to be eligible for inclusion. The same
review authors will then independently assess these for inclusion.
Any disagreements between the review authors regarding (1) which
full reports to obtain, and (2) which trials are eligible for inclusion
will be resolved by discussion. If a trial is excluded, we will keep a
record of both the report and the reason for exclusion.
We will not use a scoring system to assess the quality of each trial
but for each included trial we will collect information about:
1. the method of randomisation (including concealment of
allocation);
2. blinding (care provider, patient, outcome assessment);
3. the number of patients lost to follow-up;
4. whether the trial data were analysed according to the
principle of ’intention to treat’.
Data extraction and management
Three review authors (KBS, KOR and EB) will independently
extract data from the report of each eligible trial onto a specially
designed data extraction form. The review authors will not be
blinded to journal or institution. We will extract the following
data from each report:
• diagnostic criteria used for acute ischaemic stroke,
including whether MRI diffusion and perfusion mismatch, CT
angiography, or CT perfusion were used to identify eligible
patients;
• anatomy of the arterial occlusion;
• time interval from stroke onset to randomisation;
• time to actual delivery of percutaneous vascular or
intravenous thrombolytic therapy (not start of procedure);
• numbers of patients in each treatment group with outcome
events;
• modality of percutaneous vascular intervention used;
• precise form of pharmacological thrombolytic therapy used
(e.g. agent, dose, route of administration);
• concomitant antithrombotic therapy.
One review author (KBS) will enter the data into the Cochrane
Review Manager software, RevMan 5.1 (RevMan 2011). This will
be checked by another review author (KOR) against the hard copy
data extraction forms to correct any clerical data entry errors. If any
relevant data are missing from the available publications, we will
make direct contact with the principal investigators concerned.
Assessment of risk of bias in included studies
We will make an assessment of the risk of bias on selection of
patients into the studies by appraisal of the random sequence and
allocation concealment of the intervention, and the performance
of the studies by appraisal of the blinding of the investigator or
patient, or both, and the detection of information by blinding
of the outcome assessor and data investigator. We will appraise
the attrition bias by the number of patients lost to follow-up and
Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
patients excluded from the study, and appraise any reporting biases
in the studies. We will score these data as low risk of bias, unclear,
or high risk of bias.
Measures of treatment effect
For dichotomous outcomes, we will calculate a weighted esti-
mate of the treatment effects across trials and will report odds ra-
tios (OR) with 95% confidence intervals (CI). Where continuous
scales of measurement are used to assess the effects of treatment,
we will use the mean difference (MD). For studies that use differ-
ent scales for the assessment of similar outcomes, we will report
standardised mean differences (SMD).
Dealing with missing data
If the published information does not allow intention-to-treat
analysis we will contact the authors to get as complete follow-up
data as possible on all randomised patients for the originally pro-
posed period of follow-up. If the data about these patients remain
unavailable, we will provide a worst-case scenario analysis for the
composite outcome of ’death and severe disability’. In this sensi-
tivity analysis, it is assumed that those patients who were lost to
follow-up in the treatment group had the worst outcome while
those patients who were lost to follow-up in the control group had
the best outcome.
Assessment of heterogeneity
We will test for heterogeneity between trial results with the
Cochrane Q statistic and I2 statistic (percentage of total variation
across studies due to heterogeneity). We will also assess hetero-
geneity qualitatively.
Assessment of reporting biases
We will use funnel plots to assess reporting bias. We will also assess
funnel plots qualitatively.
Data synthesis
We will calculate a weighted estimate of the typical treatment
effect across trials by means of a fixed-effect model. In the case
of heterogeneity of treatment effects, however, we will use the
random-effects model to assess the overall treatment effects.
Subgroup analysis and investigation of heterogeneity
Where possible, we will do subgroup analyses for: concomitant
antithrombotic therapy, stroke severity, time since stroke symp-
tom onset (that is symptom onset), modality of the percutaneous
vascular intervention, dose and type of agent used for intravenous
thrombolytic treatment, and anatomy of the arterial occlusion.
We will use the method developed by Deeks for the subgroup
analyses (Deeks 2001).
4
We plan to perform sensitivity analyses for blinded versus open
RCTs and by quality of the RCT.
ACKNOWLEDGEMENTS
We thank Brenda Thomas for her help in developing the search
strategies.
REFERENCES
Additional references
Adams 2007
Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L,
Furlan A, et al.Guidelines for the early management of adults
with ischemic stroke: a guideline from the American Heart
Association/American Stroke Association Stroke Council,
Clinical Cardiology Council, Cardiovascular Radiology and
Intervention Council, and the Atherosclerotic Peripheral
Vascular Disease and Quality of Care Outcomes in Research
Interdisciplinary Working Groups. Stroke 2007;38:
1655–711.
Deeks 2001
Deeks JJ, Altman DG, Bradburn MJ. Statistical methods
for examining heterogeneity and combining results from
several studies in meta-analysis. In: Egger M, Davey Smith
G, Altman DG editor(s). Systematic Reviews in Health Care.
Meta-analysis in Context. London: BMJ Books, 2001:
285–312.
Del Zoppo 2009
del Zoppo GJ, Saver JL, Jauch EC, Adams HP Jr, the
American Heart Association/American Stroke Association.
Expansion of the time window for treatment of acute
ischemic stroke with intravenous tissue plasminogen
activator: a science advisory from the American Heart
Association/American Stroke Association. Stroke 2009;40:
2945–8.
ESO 2009
European Stroke Organisation. Guidelines for Management
of Ischaemic Stroke and Transient Ischaemic Attack 2008
(updated January 2009). http://www.eso-stroke.org/
recommendations.php?cid=9.
Hacke 2008
Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A,
Guidetti D, et al.Thrombolysis with alteplase 3 to 4.5
hours after acute ischemic stroke. New England Journal of
Medicine 2008;359:1317–29.
Higashida 2003
Higashida R, Furlan A, Roberts H, Tomsick T, Connors B,
Barr J, et al.Trial design and reporting standards for intra-
arterial cerebral thrombolysis for acute ischemic stroke.
Stroke 2003;34:e109–37.
Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Khatri 2005
Khatri P, Neff J, Broderick J, Khoury J, Carrozzella J,
Tomsick T, et al.Revascularization end points in stroke
interventional trials: recanalization versus reperfusion in
IMS-I. Stroke 2005;36:2400–3.
Mattle 2008
Mattle HP, Arnold M, Georgiadis D, Baumann C,
Nedeltchev K, Benninger D, et al.Comparison of
intraarterial and intravenous thrombolysis for ischemic
stroke with hyperdense middle cerebral artery sign. Stroke
2008;39(2):379–83.
Mielke 2009
Mielke O, Wardlaw JM, Liu M. Thrombolysis
(different doses, routes of administration and agents)
for acute ischaemic stroke. Cochrane Database of
Systematic Reviews 2009, Issue 1. [DOI: 10.1002/
14651858.CD000514.pub2]
Nedeltchev 2006
Nedeltchev K, Fischer U, Arnold M, Ballinari P, Haefeli
T, Kappeler L, et al.Long-term effect of intra-arterial
thrombolysis in stroke. Stroke 2006;37:3002–7.
Nogueira 2009
Nogueira RG, Schwamm LH, Hirsch JA. Endovascular
approaches to acute stroke, Part 1: Drugs, devices, and data.
American Journal of Neuroradiology 2009;30:649–61.
Ogawa 2007
Ogawa A, Mori E, Minematsu K, Taki W, Takahashi A,
Nemoto S, et al.Randomized trial of intraarterial infusion
of urokinase within 6 hours of middle cerebral artery stroke:
the middle cerebral artery embolism local fibrinolytic
intervention trial (MELT) Japan. Stroke 2007;38:2633–9.
RevMan 2011
The Nordic Cochrane Centre, The Cochrane Collaboration.
Review Manager (RevMan). 5.1. Copenhagen: The Nordic
Cochrane Centre, The Cochrane Collaboration, 2011.
Rosamund 2008
Rosamund W, Flegal K, Furie K, Go A, Greenlund K, Haase
N, et al.Heart disease and stroke statistics: 2008 update -
a report from the American Heart Association Statistics
Committee and Stroke Statistics Subcommittee. Circulation
2008;117:e25–146.
5
Strong 2007
Strong K, Mathers C, Bonita R. Preventing stroke: saving
lives around the world. Lancet Neurology 2007;6:182–7.
Wardlaw 2009
Wardlaw JM, Murray V, Berge E, del Zoppo GJ.
Thrombolysis for acute ischaemic stroke. Cochrane Database
of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/
14651858.CD000213.pub2]
∗
Indicates the major publication for the study

APPENDICES

Appendix 1. MEDLINE (Ovid) search strategy

1. cerebrovascular disorders/ or basal ganglia cerebrovascular disease/ or exp brain ischemia/ or carotid artery diseases/ or carotid artery
thrombosis/ or intracranial arterial diseases/ or cerebral arterial diseases/ or exp “intracranial embolism and thrombosis”/ or exp stroke/
2. (isch?emi$ adj6 (stroke$ or apoplex$ or cerebral vasc$ or cerebrovasc$ or cva)).tw.
3. ((brain or cerebr$ or cerebell$ or vertebrobasil$ or hemispher$ or intracran$ or intracerebral or infratentorial or supratentorial or
middle cerebr$ or mca$ or anterior circulation) adj5 (isch?emi$ or infarct$ or thrombo$ or emboli$ or occlus$ or hypoxi$)).tw.
4. 1 or 2 or 3
5. radiography, interventional/ or radiology, interventional/
6. catheterization/ or angioplasty/ or angioplasty, balloon/ or angioplasty, balloon, laser-assisted/ or angioplasty, laser/ or atherectomy/
or balloon dilatation/ or catheter ablation/
7. Stents/
8. thrombectomy/ or embolectomy/
9. blood vessel prosthesis/ or blood vessel prosthesis implantation/
10. Cerebral Revascularization/ or reperfusion/ or dilatation/
11. (interventional adj3 (radiolog$ or radiograph$ or neuroradiolog$)).tw.
12. (angioplast$ or stent$).tw.
13. (thrombectomy or embolectomy or atherect$).tw.
14. (thromboaspiration or arterial recanali?ation).tw.
15. ((mechanical or radiolog$ or pharmacomechanical or laser or endovascular or neurovascular) adj5 (thrombolys$ or reperfusion or
fragment$ or aspiration or recanali?ation or clot lys$)).tw.
16. ((clot or thrombus or thrombi or embol$) adj5 (aspirat$ or remov$ or retriev$ or fragment$ or retract$ or extract$ or obliterat$ or
dispers$)).tw.
17. ((retrieval or extraction) adj5 device$).tw.
18. endoluminal repair$.tw.
19. (blood vessel adj5 (prosthesis or implantat$)).tw.
20. ((merci or concentric) adj retriever).tw.
21. (endovascular snare$ or neuronet or microsnare or X-ciser or angiojet).tw.
22. ultrasonics/ or ultrasonic therapy/ or ultrasonography/ or exp ultrasonography, doppler/ or ultrasonography, interventional/
23. (ultrasound$ or ultrasonic$ or ultrasonogra$ or sonograph$ or insonation).tw.
24. ((transcranial adj5 doppler) or TCD or TCCD).tw.
25. ultrasonography.fs.
26. (sonothrombolysis or sonothromboly$ or sonolys$ or sonothrombotripsy or thrombotripsy).tw.
27. or/5-26
28. thrombolytic therapy/
Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol) 6
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
29. fibrinolytic agents/ or plasmin/ or plasminogen/ or tissue plasminogen activator/ or exp plasminogen activators/ or urokinase-type
plasminogen activator/
30. fibrinolysis/
31. (thromboly$ or fibrinoly$ or recanalis$ or recanaliz$).tw.
32. ((clot$ or thrombus) adj5 (lyse or lysis or dissolve$ or dissolution)).tw.
33. (tPA or t-PA or rtPA or rt-PA or plasminogen or plasmin or alteplase or actilyse).tw.
34. (anistreplase or streptodornase or streptokinase or urokinase or pro?urokinase or rpro?uk or lumbrokinase or duteplase or lanoteplase
or pamiteplase or reteplase or saruplase or staphylokinase or streptase).tw.
35. 28 or 29 or 30 or 31 or 32 or 33 or 34
36. 4 and 27 and 35
37. Randomized Controlled Trials as Topic/
38. random allocation/
39. Controlled Clinical Trials as Topic/
40. control groups/
41. clinical trials as topic/ or clinical trials, phase i as topic/ or clinical trials, phase ii as topic/ or clinical trials, phase iii as topic/ or
clinical trials, phase iv as topic/
42. double-blind method/
43. single-blind method/
44. Therapies, Investigational/
45. Research Design/
46. randomized controlled trial.pt.
47. controlled clinical trial.pt.
48. (clinical trial or clinical trial phase i or clinical trial phase ii or clinical trial phase iii or clinical trial phase iv).pt.
49. random$.tw.
50. (controlled adj5 (trial$ or stud$)).tw.
51. (clinical$ adj5 trial$).tw.
52. ((control or treatment or experiment$ or intervention) adj5 (group$ or subject$ or patient$)).tw.
53. (quasi-random$ or quasi random$ or pseudo-random$ or pseudo random$).tw.
54. ((control or experiment$ or conservative) adj5 (treatment or therapy or procedure or manage$)).tw.
55. ((singl$ or doubl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).tw.
56. (coin adj5 (flip or flipped or toss$)).tw.
57. latin square.tw.
58. versus.tw.
59. controls.tw.
60. or/37-59
61. 36 and 60
62. limit 61 to humans

HISTORY
Protocol first published: Issue 9, 2011

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol) 7
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
CONTRIBUTIONS OF AUTHORS
KBS: design of the review, drafting of protocol.
EB, KOR and JW: conception and design of the review, commenting on protocol drafts.

DECLARATIONS OF INTEREST
None declared

SOURCES OF SUPPORT

Internal sources
• No sources of support supplied

External sources
• South-Eastern Norway Regional Health Authority, Norway.
Educational grant

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol) 8
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.