Download PDF
Aktuelle Neurologie 2013; 40(01): 29-36
DOI: 10.1055/s-0032-1333267
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Aktuelle Studien zur Akuttherapie des Schlaganfalls

Current Acute Stroke Trials
G. Thomalla
1   Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf
,
H. B. Huttner
2   Neurologische Klinik, Universitätsklinikum Erlangen
,
M. Köhrmann
2   Neurologische Klinik, Universitätsklinikum Erlangen
› Author Affiliations
Further Information

Publication History

Publication Date:
22 January 2013 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Intravenöse Thrombolyse ist die einzige zugelassene spezifische Therapie zur Behandlung des akuten Schlaganfalls. Im vergangenen Jahr sind jedoch die Ergebnisse einiger interessanter klinischer Studien zur akuten Schlaganfalltherapie mit anderen Behandlungsansätzen publiziert worden. Darüber hinaus laufen aktuell vielversprechende klinische Schlaganfallstudien. Auf der Basis eines selektiven Reviews publizierter Daten und Studienprotokolle wird eine Übersicht über aktuelle Studien zur Akuttherapie des Schlaganfalls gegeben. Zur intravenösen Thrombolyse mit Alteplase bei Patienten außerhalb der Zulassungskriterien hat die IST-3 Studie neue Erkenntnisse gebracht. Tenecteplase hat in einer Phase 2-Studie vielversprechende Ergebnisse gezeigt. Weitere Studien laufen, welche die intravenöse Thrombolyse im erweiterten Zeitfenster ober bei Patienten mit unbekanntem Zeitfenster auf der Basis einer Patientenauswahl mittels erweiterter Bildgebungskriterien untersuchen. Eine Dynamik zeigt Studien zur endovaskulären Behandlung, getrieben durch aktuelle Studien zur mechanischen Thrombektomie mit Stent-Retriever-Systemen. Hier konnten 2 Phase 2-Studien die Überlegenheit der Stent-Retriever gegenüber dem MERCI-Device zeigen (SWIFT, TREVO-2), Phase 3-Studien mit klinischen Endpunkten sind in Vorbereitung. Auch zur Neuroprotektion beim akuten. Schlaganfall gibt es aktuelle Studien (ICTUS, AXIS-2), welche im Hinblick auf die primären Endpunkte negativ waren. Ein weiterer untersuchter Behandlungsansatz ist die hämodynamische Augmentation. Zusammenfassend sind zahlreiche Aktivitäten auf dem Feld der klinischen Studien zur akuten Schlaganfallbehandlung sind zu verzeichnen, wobei der Schwerpunkt im Bereich der auf Rekanalisation zielenden Behandlungsansätze liegt. Der Nachweis der Wirksamkeit der Behandlungsansätze steht aus. Es ist zu erwarten, dass die Ergebnisse derzeit laufender oder geplanter Studien die akute Schlaganfallbehandlung beeinflussen werden. Industrieunabhängige Investigator-initiierte klinische Studien erlangen eine größere Bedeutung.

Abstract

Intravenous thrombolysis is still the only approved treatment for acute ischaemic stroke. However, recently results of several interesting clinical studies have been reported testing different treatment approaches for acute stroke treatment. There are a number of promising clinical studies of acute stroke treatment running or in preparation. Based on a selective review of published data and study protocols we review current clinical trials of acute stroke treatment. IST-3 has brought new insights into intravenous thrombolysis with Alteplase in patients outside the approval criteria. The thrombolytic drug Tenecteplase showed promise in a recent phase 2-trial. There are also ongoing studies testing efficacy and safety of intravenous thrombolysis in an extended time-window or in patients with unknown time of symptom onset using extended imaging criteria to identify patients for treatment. Advances are observed in interventional acute stroke treatment, driven from recent studies on mechanical thrombectomy using stent retrievers. 2 studies (SWIFT, TREVO-2) have demonstrated the superiority of stent retriever devices over the MERCI device for recanalisation rates and early neurological improvement. Larger follow-up studies with clinical endpoints are in preparation. There are current trials on neuroprotection in acute stroke but both were negative as to the primary endpoints (ICTUS, AXIS-2). Haemodynamic augmentation represents another approach under study in clinical trials. In summary there are numerous encouraging activities in acute stroke treatment with a focus on strategies aiming at recanalisation. Evidence for clinical efficacy of these new approaches is still pending. The results of ongoing trials should have an impact on acute stroke treatment. The importance of industry-independent investigator-initiated clinical trials in acute stroke is growing.

Schlüsselwörter

akuter Schlaganfall - klinische Studien - Thrombolyse - mechanische Thrombektomie - Neuroprotektion

Keywords

acute stroke - clinical trials - thrombolysis - mechanical thrombectomy - neuroprotection
 

  • Literatur

  • 1 Tissue plasminogen activator for acute ischemic stroke . The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333: 1581-1587
    CrossrefPubMedGoogle Scholar
  • 2 Hacke W, Kaste M, Bluhmki E et al. Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med 2008; 359: 1317-1329
    CrossrefPubMedGoogle Scholar
  • 3 Wahlgren N, Ahmed N, Davalos A et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007; 369: 275-282
    CrossrefPubMedGoogle Scholar
  • 4 Minnerup J, Wersching H, Ringelstein EB et al. Impact of the extended thrombolysis time window on the proportion of recombinant tissue-type plasminogen activator-treated stroke patients and on door-to-needle time. Stroke 2011; 42: 2838-2843
    CrossrefPubMedGoogle Scholar
  • 5 Adeoye O, Hornung R, Khatri P et al. Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years. Stroke 2011; 42: 1952-1955
    CrossrefPubMedGoogle Scholar
  • 6 Barber PA, Zhang J, Demchuk AM et al. Why are stroke patients excluded from TPA therapy? An analysis of patient eligibility. Neurology 2001; 56: 1015-1020
    CrossrefPubMedGoogle Scholar
  • 7 Saqqur M, Molina CA, Salam A et al. Clinical deterioration after intravenous recombinant tissue plasminogen activator treatment: a multicenter transcranial Doppler study. Stroke 2007; 38: 69-74
    CrossrefPubMedGoogle Scholar
  • 8 Saver JL. Number needed to treat estimates incorporating effects over the entire range of clinical outcomes: novel derivation method and application to thrombolytic therapy for acute stroke. Arch Neurol 2004; 61: 1066-1070
    CrossrefPubMedGoogle Scholar
  • 9 Lees KR, Bluhmki E, von Kummer R et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010; 375: 1695-1703
    CrossrefPubMedGoogle Scholar
  • 10 Sandercock P, Wardlaw JM, Lindley RI et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet 2012; 379: 2352-2363
    CrossrefPubMedGoogle Scholar
  • 11 Wardlaw JM, Murray V, Berge E et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 2012; 379: 2364-2372
    CrossrefPubMedGoogle Scholar
  • 12 Parsons M, Spratt N, Bivard A et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 2012; 366: 1099-1107
    CrossrefPubMedGoogle Scholar
  • 13 Haley Jr EC, Thompson JL, Grotta JC et al. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke 2010; 41: 707-711
    CrossrefPubMedGoogle Scholar
  • 14 Fiebach JB, Al-Rawi Y, Wintermark M et al. Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase. Stroke 2012; 43: 1561-1566
    CrossrefPubMedGoogle Scholar
  • 15 Ma H, Parsons MW, Christensen S et al. A multicentre, randomized, double-blinded, placebo-controlled Phase III study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND). Int J Stroke 2012; 7: 74-80
    CrossrefPubMedGoogle Scholar
  • 16 Thomalla G, Cheng B, Ebinger M et al. DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4.5 h of symptom onset (PRE-FLAIR): a multicentre observational study. Lancet Neurol 2011; 10: 978-986
    CrossrefPubMedGoogle Scholar
  • 17 Zeumer H, Hacke W, Kolmann HL et al. Lokale Fibrinolysetherapie bei Basilaris-Thrombose. Dtsch Med Wochenschr 1982; 107: 728-731
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke 2007; 38: 967-973
    CrossrefPubMedGoogle Scholar
  • 19 Fiehler J, Soderman M, Turjman F et al. Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients: a position paper endorsed by ESMINT and ESNR: Part I: Current situation and major research questions. Neuroradiology. 2012
    PubMedGoogle Scholar
  • 20 Gralla J, Brekenfeld C, Mordasini P et al. Mechanical thrombolysis and stenting in acute ischemic stroke. Stroke 2012; 43: 280-285
    CrossrefPubMedGoogle Scholar
  • 21 Castano C, Dorado L, Guerrero C et al. Mechanical thrombectomy with the Solitaire AB device in large artery occlusions of the anterior circulation: a pilot study. Stroke 2010; 41: 1836-1840
    CrossrefPubMedGoogle Scholar
  • 22 Costalat V, Machi P, Lobotesis K et al. Rescue, combined, and stand-alone thrombectomy in the management of large vessel occlusion stroke using the solitaire device: a prospective 50-patient single-center study: timing, safety, and efficacy. Stroke 2011; 42: 1929-1935
    CrossrefPubMedGoogle Scholar
  • 23 Saver JL, Jahan R, Levy EI et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012; 380: 1241-1249
    CrossrefPubMedGoogle Scholar
  • 24 Nogueira RG, Lutsep HL, Gupta R et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 2012; 380: 1231-1240
    CrossrefPubMedGoogle Scholar
  • 25 http://www.ims3.org/ (Stand 01.12.2012)
    PubMed
  • 26 Combined intravenous and intra-arterial recanalization for acute ischemic stroke: the Interventional Management of Stroke Study. Stroke 2004; 35: 904-911
    CrossrefPubMedGoogle Scholar
  • 27 The Interventional Management of Stroke (IMS) II Study. Stroke 2007; 38: 2127-2135
    CrossrefPubMedGoogle Scholar
  • 28 Khatri P, Hill MD, Palesch YY et al. Methodology of the Interventional Management of Stroke III Trial. Int J Stroke 2008; 3: 130-137
    CrossrefPubMedGoogle Scholar
  • 29 Zaidat OO, Lazzaro MA, Gupta R et al. Interventional Management of Stroke III Trial: establishing the foundation. J Neurointerv Surg 2012; 4: 235-237
    CrossrefPubMedGoogle Scholar
  • 30 Albers GW, Thijs VN, Wechsler L et al. Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol 2006; 60: 508-517
    CrossrefPubMedGoogle Scholar
  • 31 Lansberg MG, Straka M, Kemp S et al. MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol 2012; 11: 860-867
    CrossrefPubMedGoogle Scholar
  • 32 Davalos A, Alvarez-Sabin J, Castillo J et al. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet 2012; 380: 349-357
    CrossrefPubMedGoogle Scholar
  • 33 Rosenberg G, Bornstein N, Diener HC et al. The Membrane-Activated Chelator Stroke Intervention (MACSI) Trial of DP-b99 in acute ischemic stroke: a randomized, double-blind, placebo-controlled, multinational pivotal phase III study. Int J Stroke 2011; 6: 362-367
    CrossrefPubMedGoogle Scholar
  • 34 Lin S, Liu M, Wu B et al. External counterpulsation for acute ischaemic stroke. Cochrane Database Syst Rev 2012; 1 CD009264
    PubMedGoogle Scholar
  • 35 Shuaib A, Bornstein NM, Diener HC et al. Partial aortic occlusion for cerebral perfusion augmentation: safety and efficacy of NeuroFlo in Acute Ischemic Stroke trial. Stroke 2011; 42: 1680-1690
    CrossrefPubMedGoogle Scholar
  • 36 Lampl Y, Zivin JA, Fisher M et al. Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1). Stroke 2007; 38: 1843-1849
    CrossrefPubMedGoogle Scholar
  • 37 Zivin JA, Albers GW, Bornstein N et al. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke 2009; 40: 1359-1364
    CrossrefPubMedGoogle Scholar
  • 38 Zivin JA, Sehra R, Shoshoo A et al. NeuroThera((R)) Efficacy and Safety Trial – 3 (NEST-3): a double-blind, randomized, sham-controlled, parallel group, multicenter, pivotal study to assess the safety and efficacy of transcranial laser therapy with the NeuroThera((R)) Laser System for the treatment of acute ischemic stroke within 24 h of stroke onset. Int J Stroke 2012;
    PubMedGoogle Scholar
  • 39 Thomalla G, Ebinger M, Fiehler J et al. EU-geförderte Therapiestudie WAKE-UP. Eine randomisierte, placebokontrollierte, MRT-basierte Thrombolysestudie bei „wake-up stroke“. Nervenarzt 2012; 83: 1241-1251
    CrossrefPubMedGoogle Scholar