TY - JOUR
T1 - Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage
T2 - The intraventricular hemorrhage thrombolysis trial
AU - Naff, Neal
AU - Williams, Michael A.
AU - Keyl, Penelope M.
AU - Tuhrim, Stanley
AU - Bullock, M. Ross
AU - Mayer, Stephan A.
AU - Coplin, William
AU - Narayan, Raj
AU - Haines, Stephen J
AU - Cruz-Flores, Salvador
AU - Zuccarello, Mario
AU - Brock, David
AU - Awad, Issam
AU - Ziai, Wendy C.
AU - Marmarou, Anthony
AU - Rhoney, Denise
AU - McBee, Nichol
AU - Lane, Karen
AU - Hanley, Daniel F.
PY - 2011/11
Y1 - 2011/11
N2 - BACKGROUND AND PURPOSE-: Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. METHODS-: Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. RESULTS-: Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. CONCLUSIONS-: Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment.
AB - BACKGROUND AND PURPOSE-: Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. METHODS-: Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. RESULTS-: Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. CONCLUSIONS-: Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment.
KW - intracerebral hemorrhage
KW - intraventricular hemorrhage
KW - thrombolysis
KW - tissue-type plasminogen activator
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U2 - 10.1161/STROKEAHA.110.610949
DO - 10.1161/STROKEAHA.110.610949
M3 - Article
C2 - 21868730
AN - SCOPUS:80054974583
SN - 0039-2499
VL - 42
SP - 3009
EP - 3016
JO - Stroke
JF - Stroke
IS - 11
ER -