Open AccessA multicenter, randomized, double‐blinded, placebo‐controlled phase III study of C lot L ysis E valuation of A ccelerated R esolution of I ntraventricular H emorrhage ( CLEAR III )
Author(s) -
Ziai Wendy C.,
Tuhrim Stanley,
Lane Karen,
McBee Nichol,
Lees Kennedy,
Dawson Jesse,
Butcher Kenneth,
Vespa Paul,
Wright David W.,
Keyl Penelope M.,
Mendelow A. David,
Kase Carlos,
Wijman Christine,
Lapointe Marc,
John Sayona,
Thompson Richard,
Thompson Carol,
Mayo Steven,
Reilly Pat,
Janis Scott,
Awad Issam,
Hanley Daniel F.
Publication year - 2014
Publication title -
international journal of stroke
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.375
H-Index - 74
eISSN - 1747-4949
pISSN - 1747-4930
DOI - 10.1111/ijs.12097
Subject(s) - medicine , intraventricular hemorrhage , ventriculostomy , modified rankin scale , intracerebral hemorrhage , anesthesia , placebo , fourth ventricle , external ventricular drain , thrombolysis , clinical endpoint , surgery , hydrocephalus , subarachnoid hemorrhage , randomized controlled trial , cardiology , myocardial infarction , ischemia , pathology , pregnancy , genetics , ischemic stroke , alternative medicine , biology , gestational age
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 C lot L ysis E valuation of A ccelerated R esolution of I ntraventricular H emorrhage 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 R ankin S cale 0–3 vs. 4–6 at 180 days. Clinical secondary outcomes include additional modified R ankin S cale dichotomizations at 180 days (0–4 vs. 5–6), ordinal modified R ankin S cale (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.