Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results

on behalf of the MR WITNESS Investigators

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective: Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242). Methods: Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS). Results: Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5–13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0–1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions. Interpretation: Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980–993.

Original languageEnglish (US)
Pages (from-to)980-993
Number of pages14
JournalAnnals of Neurology
Volume83
Issue number5
DOIs
StatePublished - May 1 2018

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Stroke
Intracranial Hemorrhages
Tissue Plasminogen Activator
Diffusion Magnetic Resonance Imaging
Brain Edema
Edema
Magnetic Resonance Imaging
Prospective Studies
Guidelines

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Intravenous thrombolysis in unwitnessed stroke onset : MR WITNESS trial results. / on behalf of the MR WITNESS Investigators.

In: Annals of Neurology, Vol. 83, No. 5, 01.05.2018, p. 980-993.

Research output: Contribution to journalArticle

on behalf of the MR WITNESS Investigators. / Intravenous thrombolysis in unwitnessed stroke onset : MR WITNESS trial results. In: Annals of Neurology. 2018 ; Vol. 83, No. 5. pp. 980-993.
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abstract = "Objective: Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242). Methods: Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS). Results: Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5–13.3) from when they were last known to be well. There was 1 sICH (1.3{\%}) and 3 cases of symptomatic edema (3.8{\%}). At 90 days, 39{\%} of subjects achieved mRS = 0–1, as did 48{\%} of subjects who had vessel imaging and were without large vessel occlusions. Interpretation: Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980–993.",
author = "{on behalf of the MR WITNESS Investigators} and Schwamm, {Lee H.} and Ona Wu and Song, {Shlee S.} and Latour, {Lawrence L.} and Ford, {Andria L.} and Hsia, {Amie W.} and Alona Muzikansky and Betensky, {Rebecca A.} and Yoo, {Albert J.} and Lev, {Michael H.} and Gregoire Boulouis and Arne Lauer and Pedro Cougo and Copen, {William A.} and Harris, {Gordon J.} and Steven Warach and Sidney Starkman and Ramin Zand and Drake, {Kendra W} and Carlos Kase and Raphael Carandang and Eric Searls",
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T1 - Intravenous thrombolysis in unwitnessed stroke onset

T2 - MR WITNESS trial results

AU - on behalf of the MR WITNESS Investigators

AU - Schwamm, Lee H.

AU - Wu, Ona

AU - Song, Shlee S.

AU - Latour, Lawrence L.

AU - Ford, Andria L.

AU - Hsia, Amie W.

AU - Muzikansky, Alona

AU - Betensky, Rebecca A.

AU - Yoo, Albert J.

AU - Lev, Michael H.

AU - Boulouis, Gregoire

AU - Lauer, Arne

AU - Cougo, Pedro

AU - Copen, William A.

AU - Harris, Gordon J.

AU - Warach, Steven

AU - Starkman, Sidney

AU - Zand, Ramin

AU - Drake, Kendra W

AU - Kase, Carlos

AU - Carandang, Raphael

AU - Searls, Eric

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N2 - Objective: Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242). Methods: Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS). Results: Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5–13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0–1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions. Interpretation: Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980–993.

AB - Objective: Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242). Methods: Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS). Results: Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5–13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0–1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions. Interpretation: Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980–993.

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