BACKGROUND: In adults, intraventricular thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) facilitates resolution of intraventricular haemorrhage (IVH), reduces intracranial pressure, decreases duration of cerebrospinal fluid diversion, and may ameliorate direct neural injury. We hypothesize that patients with small parenchymal haematoma volumes (<30 cc) and relatively large IVH causing acute obstructive hydrocephalus would have improved clinical outcomes when given injections of low-dose rtPA to accelerate lysis and evacuation of IVH compared with placebo. METHODS: The Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage III trial is an investigator-initiated, phase III, randomized, multicenter, double-blind, placebo-controlled study comparing the use of external ventricular drainage (EVD) combined with intraventricular injection of rtPA to EVD plus intraventricular injection of normal saline (placebo) for the treatment of IVH. Patients with known symptom onset within 24 h of the computed tomography scan confirmed IVH and third or fourth ventricle obstruction, with or without supratentorial intracerebral haemorrhage volume <30 cc, who require EVD are screened with a computed tomography scan at least six hours after EVD placement and, if necessary, at consecutive 12-h intervals until stabilization of any intracranial bleeding has been established. Patients who meet clinical and imaging criteria (no ongoing coagulopathy and no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly) will be randomized to either intraventricular rtPA or placebo. RESULTS: The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 180 days. Clinical secondary outcomes include additional modified Rankin Scale dichotomizations at 180 days (0-4 vs. 5-6), ordinal modified Rankin Scale (0-6), mortality and safety events at 30 days, mortality at 180 days, functional status measures, type and intensity of intensive care unit management, rate and extent of ventricular blood clot removal, and quality of life measures.
BACKGROUND: In adults, intraventricular thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) facilitates resolution of intraventricular haemorrhage (IVH), reduces intracranial pressure, decreases duration of cerebrospinal fluid diversion, and may ameliorate direct neural injury. We hypothesize that patients with small parenchymal haematoma volumes (<30 cc) and relatively large IVH causing acute obstructive hydrocephalus would have improved clinical outcomes when given injections of low-dose rtPA to accelerate lysis and evacuation of IVH compared with placebo. METHODS: The Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage III trial is an investigator-initiated, phase III, randomized, multicenter, double-blind, placebo-controlled study comparing the use of external ventricular drainage (EVD) combined with intraventricular injection of rtPA to EVD plus intraventricular injection of normal saline (placebo) for the treatment of IVH. Patients with known symptom onset within 24 h of the computed tomography scan confirmed IVH and third or fourth ventricle obstruction, with or without supratentorial intracerebral haemorrhage volume <30 cc, who require EVD are screened with a computed tomography scan at least six hours after EVD placement and, if necessary, at consecutive 12-h intervals until stabilization of any intracranial bleeding has been established. Patients who meet clinical and imaging criteria (no ongoing coagulopathy and no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly) will be randomized to either intraventricular rtPA or placebo. RESULTS: The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 180 days. Clinical secondary outcomes include additional modified Rankin Scale dichotomizations at 180 days (0-4 vs. 5-6), ordinal modified Rankin Scale (0-6), mortality and safety events at 30 days, mortality at 180 days, functional status measures, type and intensity of intensive care unit management, rate and extent of ventricular blood clot removal, and quality of life measures.
Authors: Andrew M Demchuk; Dar Dowlatshahi; David Rodriguez-Luna; Carlos A Molina; Yolanda Silva Blas; Imanuel Dzialowski; Adam Kobayashi; Jean-Martin Boulanger; Cheemun Lum; Gord Gubitz; Vasantha Padma; Jayanta Roy; Carlos S Kase; Jayme Kosior; Rohit Bhatia; Sarah Tymchuk; Suresh Subramaniam; David J Gladstone; Michael D Hill; Richard I Aviv Journal: Lancet Neurol Date: 2012-03-08 Impact factor: 44.182
Authors: A David Mendelow; Barbara A Gregson; Helen M Fernandes; Gordon D Murray; Graham M Teasdale; D Terence Hope; Abbas Karimi; M Donald M Shaw; David H Barer Journal: Lancet Date: 2005 Jan 29-Feb 4 Impact factor: 79.321
Authors: Daniel F Hanley; Karen Lane; Nichol McBee; Wendy Ziai; Stanley Tuhrim; Kennedy R Lees; Jesse Dawson; Dheeraj Gandhi; Natalie Ullman; W Andrew Mould; Steven W Mayo; A David Mendelow; Barbara Gregson; Kenneth Butcher; Paul Vespa; David W Wright; Carlos S Kase; J Ricardo Carhuapoma; Penelope M Keyl; Marie Diener-West; John Muschelli; Joshua F Betz; Carol B Thompson; Elizabeth A Sugar; Gayane Yenokyan; Scott Janis; Sayona John; Sagi Harnof; George A Lopez; E Francois Aldrich; Mark R Harrigan; Safdar Ansari; Jack Jallo; Jean-Louis Caron; David LeDoux; Opeolu Adeoye; Mario Zuccarello; Harold P Adams; Michael Rosenblum; Richard E Thompson; Issam A Awad Journal: Lancet Date: 2017-01-10 Impact factor: 79.321
Authors: Vahid Eslami; Pouya Tahsili-Fahadan; Lucia Rivera-Lara; Dheeraj Gandhi; Hasan Ali; Adrian Parry-Jones; Lilli S Nelson; Richard E Thompson; Saman Nekoobakht-Tak; Rachel Dlugash; Nichol McBee; Isaam Awad; Daniel F Hanley; Wendy C Ziai Journal: Stroke Date: 2019-06-10 Impact factor: 7.914
Authors: Wendy C Ziai; Nichol McBee; Karen Lane; Kennedy R Lees; Jesse Dawson; Paul Vespa; Richard E Thompson; A David Mendelow; Carlos S Kase; J Ricardo Carhuapoma; Carol B Thompson; Steven W Mayo; Pat Reilly; Scott Janis; Craig S Anderson; Mark R Harrigan; Paul J Camarata; Jean-Louis Caron; Mario Zuccarello; Issam A Awad; Daniel F Hanley Journal: Int J Stroke Date: 2019-04-03 Impact factor: 5.266
Authors: Achim Müller; W Andrew Mould; W David Freeman; Nichol McBee; Karen Lane; Rachel Dlugash; Rick Thompson; Saman Nekoovaght-Tak; Vikram Madan; Hasan Ali; Agnieszka Stadnik; Issam Awad; Daniel Hanley; Wendy C Ziai Journal: Neurocrit Care Date: 2018-08 Impact factor: 3.210