title: Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial.
abstract: OBJECTIVE
  Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke.
  
  
  METHODS
  Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion-diffusion mismatch not progressing to infarction after 1 month.
  
  
  RESULTS
  Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent (P=0.006), and National Institutes of Health Stroke Scale score on admission was lower (P=0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction (P=0.0003).
  
  
  CONCLUSIONS
  Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00975962.
authors.affiliation: From the Department of Neurology (K.D.H., N.H., P.v.W.-M., C.Z.S., D.D., H.G., K.S., P.V.R., G.A.), Department of Neuroradiology (L.S., A.N., L.Ø.), Department of Cardiology (H.E.B.), and Mobil Emergency Care Unit Aarhus (T.M.H.), Aarhus University Hospital, Aarhus, Denmark; Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark (K.D.H., N.H., D.Z., L.R.R., I.K.M., K.N., L.Ø., K.M.); Stroke Department, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, University of Lyon, Lyon, France (T.-H.C.); and Division of Cardiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada (A.N.R.).
authors.forename: Kristina Dupont
authors.initials: KD
authors.lastname: Hougaard
authors.forename: Niels
authors.initials: N
authors.lastname: Hjort
authors.forename: Dora
authors.initials: D
authors.lastname: Zeidler
authors.forename: Leif
authors.initials: L
authors.lastname: Sørensen
authors.forename: Anne
authors.initials: A
authors.lastname: Nørgaard
authors.forename: Troels Martin
authors.initials: TM
authors.lastname: Hansen
authors.forename: Paul
authors.initials: P
authors.lastname: von Weitzel-Mudersbach
authors.forename: Claus Z
authors.initials: CZ
authors.lastname: Simonsen
authors.forename: Dorte
authors.initials: D
authors.lastname: Damgaard
authors.forename: Hanne
authors.initials: H
authors.lastname: Gottrup
authors.forename: Kristina
authors.initials: K
authors.lastname: Svendsen
authors.forename: Peter Vestergaard
authors.initials: PV
authors.lastname: Rasmussen
authors.forename: Lars R
authors.initials: LR
authors.lastname: Ribe
authors.forename: Irene K
authors.initials: IK
authors.lastname: Mikkelsen
authors.forename: Kartheban
authors.initials: K
authors.lastname: Nagenthiraja
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Cho
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Redington
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Leif
authors.initials: L
authors.lastname: Østergaard
authors.forename: Kim
authors.initials: K
authors.lastname: Mouridsen
authors.forename: Grethe
authors.initials: G
authors.lastname: Andersen
mesh_terms: D000368:Aged; D000488:Allied Health Personnel; D002545:Brain Ischemia / Q000188:drug therapy / Q000628:therapy*; D002544:Cerebral Infarction / Q000453:epidemiology / Q000473:pathology; D004562:Electrocardiography; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000628:therapy; D019194:Ischemic Preconditioning / Q000009:adverse effects / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors; D016879:Salvage Therapy; D020521:Stroke / Q000188:drug therapy / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D016896:Treatment Outcome
keywords: magnetic resonance scan; neuroprotection; perconditioning; stroke