Aspiration Thrombectomy after Intravenous Alteplase Versus Intravenous Alteplase Alone

THERAPY Trial Investigators

Research output: Contribution to journalArticle

Abstract

Background and Purpose - Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear. Methods - THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany). Results - Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus intravenous: 23.9%, P=0.18) were observed. Conclusions - THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.

Original languageEnglish (US)
Pages (from-to)2331-2338
Number of pages8
JournalStroke
Volume47
Issue number9
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

Thrombectomy
Tissue Plasminogen Activator
Stents
Stroke
Safety
Intention to Treat Analysis
Intracranial Hemorrhages
Controlled Clinical Trials
Intravenous Administration
Germany
Thrombosis
Randomized Controlled Trials
Odds Ratio
Clinical Trials
Confidence Intervals
Mortality

Keywords

  • embolectomy
  • stent
  • stroke
  • thrombectomy
  • thrombolytic therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Aspiration Thrombectomy after Intravenous Alteplase Versus Intravenous Alteplase Alone. / THERAPY Trial Investigators.

In: Stroke, Vol. 47, No. 9, 01.09.2016, p. 2331-2338.

Research output: Contribution to journalArticle

THERAPY Trial Investigators. / Aspiration Thrombectomy after Intravenous Alteplase Versus Intravenous Alteplase Alone. In: Stroke. 2016 ; Vol. 47, No. 9. pp. 2331-2338.
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abstract = "Background and Purpose - Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear. Methods - THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany). Results - Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38{\%} IAT and 30{\%} intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95{\%} confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3{\%} IAT versus 9.7{\%} intravenous, P=1.0) or 90-day mortality (IAT: 12{\%} versus intravenous: 23.9{\%}, P=0.18) were observed. Conclusions - THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.",
keywords = "embolectomy, stent, stroke, thrombectomy, thrombolytic therapy",
author = "{THERAPY Trial Investigators} and J. Mocco and Zaidat, {Osama O.} and {Von Kummer}, R{\"u}diger and Yoo, {Albert J.} and Rishi Gupta and Demetrius Lopes and Don Frei and Harish Shownkeen and Ron Budzik and Ajani, {Zahra A.} and Aaron Grossman and Dorethea Altschul and Cameron McDougall and Lindsey Blake and Fitzsimmons, {Brian Fred} and Dileep Yavagal and John Terry and Jeffrey Farkas and Lee, {Seon Kyu} and Blaise Baxter and Martin Wiesmann and Michael Knauth and Donald Heck and Syed Hussain and David Chiu and Alexander, {Michael J.} and Timothy Malisch and Jawad Kirmani and Laszlo Miskolczi and Pooja Khatri",
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TY - JOUR

T1 - Aspiration Thrombectomy after Intravenous Alteplase Versus Intravenous Alteplase Alone

AU - THERAPY Trial Investigators

AU - Mocco, J.

AU - Zaidat, Osama O.

AU - Von Kummer, Rüdiger

AU - Yoo, Albert J.

AU - Gupta, Rishi

AU - Lopes, Demetrius

AU - Frei, Don

AU - Shownkeen, Harish

AU - Budzik, Ron

AU - Ajani, Zahra A.

AU - Grossman, Aaron

AU - Altschul, Dorethea

AU - McDougall, Cameron

AU - Blake, Lindsey

AU - Fitzsimmons, Brian Fred

AU - Yavagal, Dileep

AU - Terry, John

AU - Farkas, Jeffrey

AU - Lee, Seon Kyu

AU - Baxter, Blaise

AU - Wiesmann, Martin

AU - Knauth, Michael

AU - Heck, Donald

AU - Hussain, Syed

AU - Chiu, David

AU - Alexander, Michael J.

AU - Malisch, Timothy

AU - Kirmani, Jawad

AU - Miskolczi, Laszlo

AU - Khatri, Pooja

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background and Purpose - Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear. Methods - THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany). Results - Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus intravenous: 23.9%, P=0.18) were observed. Conclusions - THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.

AB - Background and Purpose - Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear. Methods - THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany). Results - Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus intravenous: 23.9%, P=0.18) were observed. Conclusions - THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.

KW - embolectomy

KW - stent

KW - stroke

KW - thrombectomy

KW - thrombolytic therapy

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DO - 10.1161/STROKEAHA.116.013372

M3 - Article

VL - 47

SP - 2331

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JO - Stroke

JF - Stroke

SN - 0039-2499

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