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Publications

Journal Article Randomized Controlled Trial Multicenter Study Clinical Trial, Phase III Clinical Trial, Phase II Ppublish

PubMed: 42044230 DOI: 10.1161/STROKEAHA.125.052935

Glenzocimab Efficacy and Safety Added to Intravenous Thrombolysis With or Without Mechanical Thrombectomy in Patients With Acute Ischemic Stroke-ACTISAVE: A Prospective, Randomized, Double-Blind Study.

Stroke 57(5):1116-1125

Authors: Martin Köhrmann, Jörg Berrouschot, Joaquín Serena, Natan M Bornstein, Helle K Iversen, Dheeraj Kalladka, Georgi Krastev, Carlos A Molina, André Peeters, Daniel Šaňák, Igor P Sibon, Lucie Della Schiava, José I Tembl, Jaime Masjuan, Hassan Soda, Sébastien Richard, Zuzana Eichlova, Alexandra L Czap, Gilles Avenard, Sophie Binay, Sirine Bougamra, Andrea Comenducci, Elodie Drumez, Adeline Meilhoc, Yannick Pletan, Anouar Sari, Elie Toledano, Jean-Marie Grouin, James C Grotta

Affiliations

  • Department of Neurology, Universitätsklinikum Essen (AöR), Klinik für Neurologie, Germany (M.K.).
  • Department of Neurology, Klinikum Altenburger Land, Altenburg, Germany (J.B.).
  • Neurology Service, Stroke Unit, Hospital Universitari de Girona Doctor Josep Trueta, Spain (J.S.).
  • Brain Division, Shaare Zedek Medical Center, Jerusalem, Israel (N.M.B.).
  • Clinical Stroke Research Unit, Department of Neurology, University Hospital -Rigshospitalet (H.K.I.), University of Copenhagen, Denmark.
  • Department of Clinical Medicine Faculty of Health and Medical Sciences (H.K.I.), University of Copenhagen, Denmark.
  • Department of Brain Sciences, Imperial College London, United Kingdom (D.K.).
  • Department of Neurology, Slovak Medical University, Bratislava and faculty Hospital Trnava (G.K.).
  • Stroke Unit, Hospital Vall d'Hebron, Barcelona, Spain (C.A.M.).
  • Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium (A.P.).
  • Department of Neurology, Comprehensive Stroke Center, University Hospital Olomouc, Czech Republic (D.S.).
  • Stroke Unit, CHU Bordeaux Hospital Pellegrin, France (I.P.S.).
  • Service de Neurologie Vasculaire, Hôpital Roger Salengro, CHRU de Lille, France (L.D.S.).
  • Servicio Neurología/ Neurology, Hospital Universitari i Politècnic La Fe/La Fe University and Polytechnic Hospital of Valenciaa/ Neurology, Hospital Universitari i Politcnic La Fe/La Fe University and Polytechnic Hospital of Valencia, Spain (J.I.T.).
  • Servicio de Neurología, Departamento de Medicina, Hospital Universitario Ramón y Cajal. Facultad de Medicina, Universidad de Alcalá. IRYCISn y Cajal. Facultad de Medicina, Universidad de Alcal. IRYCIS, Madrid, Spain (J.M.).
  • AKlinik für Akutneurologie mit Überregionaler Stroke Unit, Klinischer Neurophysiologie und Intensivmedizin, Rhön-Klinikum Campus Bad Neustadtr Akutneurologie mit berregionaler Stroke Unit, Klinischer Neurophysiologie und Intensivmedizin, Rhön-Klinikum Campus Bad Neustadt, Germany (H.S.).
  • Neurology Stroke Unit, University Hospital Centre Nancy, France (S.R.).
  • Department of Neurosurgery, Regional Hospital Liberec, Czech Republic (Z.E.).
  • Department of Neurology, Memorial Hermann Hospital-Texas Medical Center, Clinical Innovation and Research Institute, Houston (A.L.C. J.C.G.).
  • Acticor Biotech, Paris, France (G.A. S. Binay, S. Bougamra, A.C. A.M. Y.P. A.S. E.T.).
  • Aixial, Boulogne-Billancourt, France (E.D.).
  • Département de Psychologie, University of Rouen, France (J.-M.G.).

Abstract

BACKGROUND

Glenzocimab, a platelet glycoprotein VI antagonist, is a novel agent that inhibits platelet activation and aggregation. Its safety was demonstrated in the ACTIMIS trial (Acute Ischemic Stroke Interventional Study; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03803007) for patients with stroke receiving thrombolysis, with or without mechanical thrombectomy, and results suggested a reduction in intracranial hemorrhages and mortality. The ACTISAVE trial was designed as a confirmatory study to evaluate the efficacy and safety of glenzocimab in acute ischemic stroke.

METHODS

ACTISAVE (Acute Ischemic Stroke Study Evaluating Glenzocimab Used as Add-On Therapy Versus Placebo) was an international, randomized, double-blind, placebo-controlled phase 2/3 study in patients with stroke, treated by thrombolysis within 4.5 hours of symptoms onset with or without mechanical thrombectomy. The study was conducted at 54 primary and comprehensive stroke centers located in 10 countries. Patients were randomized 1:1 to glenzocimab (1000 mg-IV) or placebo. The primary outcome was the modified Rankin Scale (mRS) score of 4 to 6 at day 90. Key secondary outcome was the mRS score of 0 to 2 at day 90. Mortality, mRS shift, National Institutes of Health Stroke Scale score, quality of life, and safety outcomes were assessed.

RESULTS

Between September 2021 and October 2023, 438 patients were randomized, 421 treated, and included as randomized in the primary analysis set. Median age was 73 (63-80) years, and 43% were female. Thrombolysis was performed 2.3 hours (median) after symptom onset and followed by mechanical thrombectomy in 36% of patients. The assigned treatment began a median of 1.2 (interquartile range, 0.8-1.6) hours after thrombolysis initiation. Prethrombolysis National Institutes of Health Stroke Scale score median was 9 (6-15). At day 90, there was no statistically significant difference in the primary outcome between the treatment groups: the incidence of poor outcome (mRS score 4-6 versus 0-3) was 21.6% in the glenzocimab group compared with 15.3% placebo group (odds ratio, 1.51 [95% CI, 0.90-2.54]; P=0.120). No statistically significant difference in secondary outcomes was observed. There were no major safety signals with any intracerebral hemorrhage occurring respectively in 60 (28.6%) and 63 (29.9%) patients in glenzocimab and placebo arms.

CONCLUSIONS

ACTISAVE failed to confirm a beneficial effect of glenzocimab on mRS in patients with acute ischemic stroke treated by thrombolysis.

REGISTRATION

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05070260.

MeSH

Safety, Hemorrhage, Ischemic Stroke, Stroke, Tissue Plasminogen Activator, Double-Blind Method, Cerebrovascular Circulation, Cerebrovascular Disorders, Therapeutics, Blood Platelets, Thrombectomy