title: A randomised controlled trial of antiplatelet therapy in combination with Rt-PA thrombolysis in ischemic stroke: rationale and design of the ARTIS-Trial.
abstract: BACKGROUND
  Thrombolysis with intravenous rt-PA is currently the only approved acute therapy for ischemic stroke. Re-occlusion after initial recanalization occurs in up to 34% in patients treated with rt-PA, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolysis and antiplatelet therapy leads to a greater reduction of mortality compared to thrombolysis alone. In patients with acute ischemic stroke, several studies showed that patients already on antiplatelet treatment prior to thrombolysis had an equal or even better outcome compared to patients without prior antiplatelet treatment, despite an increased risk of intracerebral bleeding. Based on the fear of intracerebral haemorrhage, current international guidelines recommend postponing antiplatelet therapy until 24 hours after thrombolysis. Remarkably, prior use of antiplatelet therapy is not a contra-indication for thrombolysis. We hypothesize that antiplatelet therapy in combination with rt-PA thrombolysis will improve outcome by enhancing fibrinolysis and preventing re-occlusion.
  
  
  METHODS
  ARTIS is a randomised multi-center controlled trial with blind endpoint assessment. Our objective is to investigate whether immediate addition of aspirin to rt-PA thrombolysis improves functional outcome in ischemic stroke. Patients with acute ischemic stroke eligible for rt-PA thrombolysis are randomised to receive 300 mg aspirin within 1.5 hours after start of thrombolysis or standard care, consisting of antiplatelet therapy after 24 hours. Primary outcome is poor functional health at 3 months follow-up (modified Rankin Scale 3 - 6).
  
  
  CONCLUSIONS
  This is the first clinical trial investigating the combination of rt-PA and acute aspirin by means of a simple and cheap adjustment of current antiplatelet regimen. We expect the net benefit of improved functional outcome will overcome the possible slightly increased risk of intracerebral haemorrhage.
  
  
  BACKGROUND
  The Netherlands National Trial Register NTR822. The condensed rationale of the ARTIS-Trial has already been published in Cerebrovascular Diseases.
authors.affiliation: Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands. s.m.zinkstok@amc.uva.nl
authors.forename: S M
authors.initials: SM
authors.lastname: Zinkstok
authors.forename: M
authors.initials: M
authors.lastname: Vermeulen
authors.forename: J
authors.initials: J
authors.lastname: Stam
authors.forename: R J
authors.initials: RJ
authors.lastname: de Haan
authors.forename: Y B
authors.initials: YB
authors.lastname: Roos
mesh_terms: D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D009426:Netherlands; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012107:Research Design; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D001241:Aspirin
references.citation: Cerebrovasc Dis. 2007;24(1):56-65
references.pmid: 17519545
references.citation: Stroke. 2005 Jul;36(7):1452-6
references.pmid: 15947260
references.citation: Cerebrovasc Dis. 2003;16(3):183-90
references.pmid: 12865603
references.citation: Stroke. 2001 Mar;32(3):661-8
references.pmid: 11239184
references.citation: Cerebrovasc Dis. 2008;26(2):126-33
references.pmid: 18560215
references.citation: Arch Neurol. 2008 May;65(5):607-11
references.pmid: 18332238
references.citation: Stroke. 2000 Jul;31(7):1555-60
references.pmid: 10884453
references.citation: Neurology. 2002 Sep 24;59(6):862-7
references.pmid: 12297567
references.citation: Circulation. 1997 Jun 3;95(11):2508-16
references.pmid: 9184581
references.citation: Health Qual Life Outcomes. 2005 Dec 29;3:83
references.pmid: 16381611
references.citation: Stroke. 2008 Dec;39(12):3316-22
references.pmid: 18927461
references.citation: N Engl J Med. 2008 Sep 25;359(13):1317-29
references.pmid: 18815396
references.citation: Stroke. 2006 Jul;37(7):1798-804
references.pmid: 16763191
references.citation: Cerebrovasc Dis. 2010;29(1):79-81
references.pmid: 19907167
references.citation: Lancet. 2007 Jan 27;369(9558):275-82
references.pmid: 17258667
references.citation: Lancet. 2004 Mar 6;363(9411):768-74
references.pmid: 15016487
references.citation: Lancet. 1988 Aug 13;2(8607):349-60
references.pmid: 2899772
references.citation: Stroke. 2001 Dec 1;32(12):2821-7
references.pmid: 11739980
references.citation: Circulation. 1999 Jun 15;99(23):3050-5
references.pmid: 10368124
references.citation: Lancet. 1995 Dec 9;346(8989):1509-14
references.pmid: 7491044
references.citation: Circulation. 2002 Apr 9;105(14):1679-85
references.pmid: 11940547
references.citation: Stroke. 1999 Oct;30(10):2101-4
references.pmid: 10512913
references.citation: Circulation. 2007 May 22;115(20):e478-534
references.pmid: 17515473
references.citation: Cochrane Database Syst Rev. 2003;(3):CD000213
references.pmid: 12917889
references.citation: Stroke. 2007 Jan;38(1):69-74
references.pmid: 17138949
references.citation: Stroke. 2007 May;38(5):1639-40
references.pmid: 17379817
references.citation: Clin Cardiol. 2000 Sep;23(9):697-700
references.pmid: 11016021
references.citation: N Engl J Med. 1995 Dec 14;333(24):1581-7
references.pmid: 7477192
references.citation: Stroke. 2007 Mar;38(3):967-73
references.pmid: 17272772
references.citation: Circulation. 1991 Jan;83(1):170-5
references.pmid: 1898641
references.citation: Circulation. 1993 Oct;88(4 Pt 1):1484-94
references.pmid: 8403296