J Mocco1, Osama O Zaidat2, Rüdiger von Kummer2, Albert J Yoo2, Rishi Gupta2, Demetrius Lopes2, Don Frei2, Harish Shownkeen2, Ron Budzik2, Zahra A Ajani2, Aaron Grossman2, Dorethea Altschul2, Cameron McDougall2, Lindsey Blake2, Brian-Fred Fitzsimmons2, Dileep Yavagal2, John Terry2, Jeffrey Farkas2, Seon Kyu Lee2, Blaise Baxter2, Martin Wiesmann2, Michael Knauth2, Donald Heck2, Syed Hussain2, David Chiu2, Michael J Alexander2, Timothy Malisch2, Jawad Kirmani2, Laszlo Miskolczi2, Pooja Khatri2. 1. From the Mount Sinai Health System, New York, NY (J.M.); St. Vincent Mercy Medical Center, Toledo, OH (O.O.Z.); Universitätsklinikum Carl Gustav Carus, Dresden, Germany (R.v.K.); Texas Stroke Institute, Plano (A.J.Y.); WellStar Health System, Marietta, GA (R.G.); Rush University, Chicago, IL (D.L.); Swedish Medical Center, Denver, CO (D.F.); Central DuPage Hospital, Winfield, IL (H.S.); Riverside Methodist Hospital, Columbus, OH (R.B.); Kaiser Los Angeles, CA (Z.A.A.); St. Joseph's Regional Medical Center, Paterson, NJ (A.G., D.A.); St. Joseph's BNI, Phoenix, AZ (C.M.); Sunrise Hospital and Medical Center, Las Vegas, NV (L.B.); Medical College of Wisconsin, Milwaukee (B.-F.F.); University of Miami Health System, FL (D.Y.); Premier Clinical Neuroscience Institute, Dayton, OH (J.T.); Lutheran Medical Center, Brooklyn, NY (J.F.); University of Chicago Medical Center, IL (S.K.L.); Erlanger Health System, Chattanooga, TN (B.B.); Universitätsklinikum Aachen, Germany (M.W.); Universitätsmedizin Göttingen, Germany (M.K.); Forsyth Medical Center, Winston-Salem, NC (D.H.); Sparrow Hospital, Lansing, MI (S.H.); Houston Methodist Hospital, TX (D.C.); Cedars-Sinai Medical Center, Los Angeles, CA (M.J.A.); Alexian Brothers, Elk Grove, IL (T.M.); The Valley Hospital, Ridgewood, NJ (D.A.); JFK Medical Center, Edison, NJ (J.K.); Holy Cross, Fort Lauderdale, FL (L.M.); and University of Cincinnati, OH (P.K.). j.mocco@mountsinai.org. 2. From the Mount Sinai Health System, New York, NY (J.M.); St. Vincent Mercy Medical Center, Toledo, OH (O.O.Z.); Universitätsklinikum Carl Gustav Carus, Dresden, Germany (R.v.K.); Texas Stroke Institute, Plano (A.J.Y.); WellStar Health System, Marietta, GA (R.G.); Rush University, Chicago, IL (D.L.); Swedish Medical Center, Denver, CO (D.F.); Central DuPage Hospital, Winfield, IL (H.S.); Riverside Methodist Hospital, Columbus, OH (R.B.); Kaiser Los Angeles, CA (Z.A.A.); St. Joseph's Regional Medical Center, Paterson, NJ (A.G., D.A.); St. Joseph's BNI, Phoenix, AZ (C.M.); Sunrise Hospital and Medical Center, Las Vegas, NV (L.B.); Medical College of Wisconsin, Milwaukee (B.-F.F.); University of Miami Health System, FL (D.Y.); Premier Clinical Neuroscience Institute, Dayton, OH (J.T.); Lutheran Medical Center, Brooklyn, NY (J.F.); University of Chicago Medical Center, IL (S.K.L.); Erlanger Health System, Chattanooga, TN (B.B.); Universitätsklinikum Aachen, Germany (M.W.); Universitätsmedizin Göttingen, Germany (M.K.); Forsyth Medical Center, Winston-Salem, NC (D.H.); Sparrow Hospital, Lansing, MI (S.H.); Houston Methodist Hospital, TX (D.C.); Cedars-Sinai Medical Center, Los Angeles, CA (M.J.A.); Alexian Brothers, Elk Grove, IL (T.M.); The Valley Hospital, Ridgewood, NJ (D.A.); JFK Medical Center, Edison, NJ (J.K.); Holy Cross, Fort Lauderdale, FL (L.M.); and University of Cincinnati, OH (P.K.).
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.
RCT Entities:
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.
Authors: Volker Maus; Daniel Behme; Christoph Kabbasch; Jan Borggrefe; Ioannis Tsogkas; Omid Nikoubashman; Martin Wiesmann; Michael Knauth; Anastasios Mpotsaris; Marios Nikos Psychogios Journal: Clin Neuroradiol Date: 2017-02-13 Impact factor: 3.649
Authors: Heinrich P Mattle; Carl Scarrott; Mairsil Claffey; John Thornton; Juan Macho; Christian Riedel; Michael Söderman; Alain Bonafé; Michel Piotin; John Newell; Tommy Andersson Journal: Interv Neuroradiol Date: 2018-12-18 Impact factor: 1.610
Authors: D Sacks; B Baxter; B C V Campbell; J S Carpenter; C Cognard; D Dippel; M Eesa; U Fischer; K Hausegger; J A Hirsch; M S Hussain; O Jansen; M V Jayaraman; A A Khalessi; B W Kluck; S Lavine; P M Meyers; S Ramee; D A Rüfenacht; C M Schirmer; D Vorwerk Journal: AJNR Am J Neuroradiol Date: 2018-05-17 Impact factor: 3.825
Authors: Laurent Pierot; Mahesh V Jayaraman; Istvan Szikora; Joshua A Hirsch; Blaise Baxter; Shigeru Miyachi; Jeyaledchumy Mahadevan; Winston Chong; Peter J Mitchell; Alan Coulthard; Howard A Rowley; Pina C Sanelli; Donatella Tampieri; Patrick A Brouwer; Jens Fiehler; Naci Kocer; Pedro Vilela; Alex Rovira; Urs Fischer; Valeria Caso; Bart van der Worp; Nobuyuki Sakai; Yuji Matsumaru; Shin-Ichi Yoshimura; Rene Anxionnat; Hubert Desal; Luisa Biscoito; José Manuel Pumar; Orlando Diaz; Justin F Fraser; Italo Linfante; David S Liebeskind; Raul G Nogueira; Werner Hacke; Michael Brainin; Bernard Yan; Michael Soderman; Allan Taylor; Sirintara Pongpech; Michihiro Tanaka; Terbrugge Karel Journal: Interv Neuroradiol Date: 2018-10-23 Impact factor: 1.610
Authors: Laurent Pierot; Mahesh V Jayaraman; Istvan Szikora; Joshua A Hirsch; Blaise Baxter; Shigeru Miyachi; Jeyaledchumy Mahadevan; Winston Chong; Peter J Mitchell; Alan Coulthard; Howard A Rowley; Pina C Sanelli; Donatella Tampieri; Patrick A Brouwer; Jens Fiehler; Naci Kocer; Pedro Vilela; Alex Rovira; Urs Fischer; Valeria Caso; Bart van der Worp; Nobuyuki Sakai; Yuji Matsumaru; Shin-Ichi Yoshimura; Rene Anxionnat; Hubert Desal; Luisa Biscoito; José Manuel Pumar; Orlando Diaz; Justin F Fraser; Italo Linfante; David S Liebeskind; Raul G Nogueira; Werner Hacke; Michael Brainin; Bernard Yan; Michael Soderman; Allan Taylor; Sirintara Pongpech; Michihiro Tanaka; Karel Terbrugge Journal: AJNR Am J Neuroradiol Date: 2018-11 Impact factor: 3.825