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Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke (Protocol)

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

Bruins Slot KMH, Berge E, O’Rourke K, Wardlaw JM This is a reprint of a Cochrane

This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 9

Library 2011, Issue 9 http://www.thecochranelibrary.com Percutaneous vascular interventions versus intravenous t
Library 2011, Issue 9 http://www.thecochranelibrary.com Percutaneous vascular interventions versus intravenous t

T A B L E O F C O N T E N T S

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ABSTRACT

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BACKGROUND

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OBJECTIVES

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METHODS

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ACKNOWLEDGEMENTS

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REFERENCES

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5

APPENDICES

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6

. CONTRIBUTIONS OF AUTHORS

HISTORY

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DECLARATIONS OF INTEREST

 

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8

SOURCES OF SUPPORT

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8

[Intervention Protocol]

Percutaneous vascular interventions versus intravenous thrombolytic treatment for acute ischaemic stroke

Karsten MH Bruins Slot 1 , Eivind Berge 2 , Killian O’Rourke 3 , Joanna M Wardlaw 4

1 Department of Internal Medicine, Oslo University Hospital U llevål, 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 Inter nal 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.

A B S T R A C T

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.

B A C K G R O U N D

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 ar tery, leading to recanalisation and restoration of distal cerebral blood flow and an improved functional outcome.

Prompt intravenous administration of recombinant tissue pl as- minogen activator (rtPA) is an effective treatment for selected pa- tients with acute ischaemic stroke and is currently the treatme nt 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 ar tery 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 th e 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 categorie s 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 cathe ter to aspirate the thrombus; sonothrombolysis devices use ultr asonic vibrations to dissolve a thrombus; and stent devices which aim to restore cerebral blood flow by entrapping the thrombus betwee n the stent and the blood vessel.

Description of the condition

Ischaemic stroke is one of the major causes of death and disabil ity 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 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 pre clude 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 disadvantage s 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 thrombol ytic 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 al l RCTs that directly compare percutaneous vascular interventions with intravenous thrombolytic treatment.

O B J E C T I V E S

The objective of this review is to assess the safety and effectiveness of percutaneous vascular interventions compared with intrave nous thrombolytic treatment for acute ischaemic stroke.

M E T H O D S

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs) that directly compare a per - cutaneous vascular intervention with intravenous thromboly tic treatment in patients with acute ischaemic stroke.

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 re vas- cularisation in acute ischaemic stroke, including but not confine d to:

endovascular thrombectomy (retriever devices);

thromboaspiration;

mechanical fragmentation of the thrombus;

implantation of stents;

intra-arterial sonothrombolysis.

The comparison therapy will be intravenous thrombolytic tre at- 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.

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 wil l 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 sear ches. We will obtain full paper copies of those trial reports which, f rom

the title and abstract, appear to be eligible for inclusion. Th e same review authors will then independently assess these for incl usion.

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

patients excluded from the study, and appraise any reporting biases in the studies. We will score these data as low risk of bias, uncl ear, 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 treatme nt, 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-tre at analysis we will contact the authors to get as complete follow-up data as possible on all randomised patients for the original ly pro- posed period of follow-up. If the data about these patients re main unavailable, we will provide a worst-case scenario analysis for the composite outcome of ’death and severe disability’. In this se nsi- tivity analysis, it is assumed that those patients who were l ost to follow-up in the treatment group had the worst outcome while those patients who were lost to follow-up in the control group h ad the best outcome.

Assessment of heterogeneity

We will test for heterogeneity between trial results with th e Cochrane Q statistic and I 2 statistic (percentage of total variation across studies due to heterogeneity). We will also assess hete ro- 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 ).

We plan to perform sensitivity analyses for blinded versus open RCTs and by quality of the RCT.

A C K N O W L E D G E M E N T S

We thank Brenda Thomas for her help in developing the search strategies.

R E F E R E N C E S

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.

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.

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

A P P E N D I C E S

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 cerebr ovasc$ or cva)).tw.

3. ((brain or cerebr$ or cerebell$ or vertebrobasil$ or hemisphe r$ 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 impl antation/

10. Cerebral Revascularization/ or reperfusion/ or dilatation/

11. (interventional adj3 (radiolog$ or radiograph$ or neuror adiolog$)).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 obliter at$ 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/

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 alte plase 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) adj 5 (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

H I S T O R Y

Protocol first published: Issue 9, 2011

C O N T R I B U T I O N S O F A U T H O R S

KBS: design of the review, drafting of protocol.

EB, KOR and JW: conception and design of the review, commenting on protocol drafts.

D E C L A R A T I O N S O F I N T E R E S T

None declared

S O U R C E S O F S U P P O R T

Internal sources

No sources of support supplied

External sources

South-Eastern Norway Regional Health Authority, Norway. Educational grant