study by lindash


									      Study              Methods               Setting            Participants        Intervention                Outcome/Results                 Note              Reference
                                                                                                           At 3 months
                                                                                                           Cerebral infarction: 34%
                        Double blind                            554 patients any                                                         Triple H therapy was
                                              4 regional                           Nimodipine 60 mg        RR with nimodipine (95%,
  Pickard et al.          placebo-                              WFNS grade                                                               not part of routine
                                            neurosurgical                          po vs. placebo for      CI 13% to 50%)                                              12
      1989               controlled                             within 96 hours                                                          management of
                                             units in UK                           21 days                 Poor outcome: 40% RR
                        randomized                              of SAH                                                                   vasospasm
                                                                                                           with nimodipine (95%, CI
                                                                                                           20% to 55%)
                                                                                                           During treatment period       Significantly more
                                                                                                           Symptomatic vasospasm:        patients in the
                        Double blind                                               Nicardipine
                                          41 neurosurgical      906 patients                               reduced with nicardipine      placebo group were
                          placebo-                                                 0.15mg/Kg/hr
Haley et al. 1993                         centers in North      within 7 days of                           (32% vs. 46%, p<0.001         treated with triple H         65
                         controlled                                                infusion or placebo
                                              America           SAH                                        At 3 months                   therapy and received
                        randomized                                                 for 14 days
                                                                                                           Outcome: GOS similar          antihypertensive
                                                                                                           between groups                agents
                                                                                                               Between day 7 and 11
                                                                   224 and 249         Nicardipine
                                                                                                                Moderate to severe        Significantly more
                                                                  patients who        0.15mg/Kg/hr
                                                                                                           angiographic vasospasm:           patients in the
                        Double blind                            respectively had   infusion or placebo
                                          41 neurosurgical                                                     51% placebo vs. 33%        placebo group were
                          placebo-                                   cerebral          for 14 days.
Haley et al. 1993                         centers in North                                                  treatment group (p<0.01)     treated with triple H         64
                         controlled                              angiogram and           Cerebral
                                              America                                                       TCD-defined vasospasm        therapy and received
                        randomized                                TCD between        angiogram and
                                                                                                            (MFV>120cm/sec): 49%            antihypertensive
                                                                  day 7 and 11      TCD between day
                                                                                                           placebo vs. 23% treatment             agents
                                                                 following SAH           7 and 11
                                                                                                                  group (p<0.001)
                                                                                                               During initial 14 days
                                                                                                                    Clinical and
                                                                                                           angiographic vasospasm:
                                                                                   Tirilazad Mesylate          similar incidence and
                        Double blind
                                          54 neurosurgical       897 patients       2mg/Kg, 6mg/Kg           severity between groups       All patients were
Haley et al. 1997                         centers in North      within 48 hours      daily or placebo                At 3 months           treated with oral           69
                                              America               of SAH         (citrate vehicle) for   Mortality rate, favorable          nimodipine
                                                                                          10 days              outcome (GOS) and
                                                                                                               employment status:
                                                                                                              similar between groups
                                                                                                                     At 3 months            All patients were
                                                                                                           Symptomatic vasospasm:              treated with
                                                                                                            non-significantly reduced          intravenous
                                                                                   Tirilazad Mesylate
                                                                                                             in 6mg/Kg compared to       nimodipine. Tirilazad
                        Double blind       41 neurosurgical       1023 patients                             vehicle group (p=0.048).       was well tolerated.
                                                                                       2mg/Kg or
                          vehicle-        centers in Europe,    any WFNS grade                                 Mortality: reduced in      Benefits of Tirilazad
Kassell et al. 1996                                                                 6mg/Kg daily or                                                                    70
                         controlled         Australia, and       within 48 hours                               6mg/Kg compared to        predominantly shown
                                                                                    placebo (citrate
                        randomized          New Zealand              of SAH                                   vehicle group (p=0.01)           in men. No
                                                                                     vehicle) for 10
                                                                                                             Good recovery (GOS):        statistically beneficial
                                                                                                              occurred more often in      effect shown for the
                                                                                                               6mg/Kg compared to            0.6mg/Kg and
                                                                                                              vehicle group (p=0.01)      2mg/Kg dose groups
                                                                                                                     At 3 months
                                                                                                                 Mortality rate and
                                                                                                            overall outcome (GOS):
                                                                                                              similar between groups
                                           56 neurosurgical                        Tirilazad Mesylate      Symptomatic vasospasm:         Significantly more
                        Double blind                            819 women any
                                          centers in Europe,                       15mg/Kg daily or         33.7% placebo vs. 24.8%         patients in the
  Lanzino et al.          vehicle-                               WFNS grade
                                            Australia, New                          placebo (citrate            treatment group (p =     placebo group were            72
     1999                controlled                             within 48 hours
                                             Zealand, and                            vehicle) for 10                    0.005)           treated with triple H
                        randomized                                 of SAH.
                                             South Africa                                 days                                                  therapy
                                                                                                                Clinical cerebral
                                                                                                            infarction: 13% placebo
                                                                                                           vs. 8% treatment group (p
                                                                                                                     < 0.04)
                                                                                                                  At 3 months
                                                                                                              Mortality rate: 24.6%
                                                                                   Tirilazad Mesylate          among patients with       Mortality rate among
                        Double blind                            823 women any
                                          65 neurosurgical                         15mg/Kg daily or        WFNS grade IV and V vs.        groups was similar
  Lanzino et al.          vehicle-                                WFNS grade
                                          centers in North                          placebo (citrate       43.4% in placebo group (p     when entire patient           71
     1999                controlled                             SAH within 48
                                              America                                vehicle) for 10                = 0.016.                population was
                        randomized                               hours of SAH.
                                                                                          days                 Favorable outcome              considered
                                                                                                             (GOS): similar between
                                                                                                                                           All patients were
                                                                                                                                            treated with oral
                                                                                   Tirilazad Mesylate
                      Phase II, double-                                                                                                        nimodipine.
                       blind, vehicle-                           245 patients                                                                A trend toward
                                                                                       2mg/Kg or
                         controlled,       12 neurosurgical     WFNS grade I-                                No serious side effects        improvement in
Haley et al. 1995                                                                   6mg/Kg daily or                                                                    73
                      sequential dose-    centers in Canada      IV within 72                                   were identified             overall 3-month
                                                                                    placebo (citrate
                         escalation                             hours of SAH                                                             outcome (GOS) was
                                                                                     vehicle) for 10
                        randomized                                                                                                        seen in the 2 mg/kg
                                                                                                                                              per day group
                                                                                                                                         compared to placebo
                                                                                   hemodilution fluid
                                                                                                                                         All patients received
                                                                                        therapy vs
                                                                                      normovolemic                   At 1 year
                                                                32 patients Hunt                                                         nimodipine between
                                                                                      fluid therapy.          Clinical and TCD-
                        Prospective                              and Hess grade                                                          day 1 and 12. Costs
                                            Single center                           (Crystalloids and         defined vasospasm:
 Egge et al. 2001       randomized                               I-III within 72                                                           were higher and             77
                                               study                               albumin). Therapy       similar in both groups (non
                         controlled                               hours of SAH                                                           complications were
                                                                                   titrated to CVP 8-          blinded evaluation)
                                                                  (post surgery)                                                         more frequent in the
                                                                                    12cmH2O, MAP
                                                                                     20mmHg higher
                                                                                                                                            therapy group
                                                                                    than preoperative

                                                                                                            Mean global CBF (serial
                                                                                       Prophylactic            133
                                                                                                                   Xe clearance) and
                                                                82 patients Hunt    hypervolemic vs
                                                                                                               incidence of clinical        Cardiac filling
                                                                 and Hess grade       normovolemic
                        Prospective,                                                                            vasospasm similar         pressures and fluid
 Lennihan et al.                            Single center         I-IV. Surgery    fluid management
                        randomized                                                                               between groups.         intake significantly          78
     2000                                      study                performed          for 14 days.
                         controlled                                                                         Change in blood volume           higher in the
                                                                within 6 days of         (Isotonic
                                                                                                             (chromium55 tagged red      hypervolemic group
                                                                      SAH            crystalloids and
                                                                                                            blood cells method) also
                                                                                                             similar between groups
                                                                                                              Between day 7 and 11
                                                                                     rt-PA 10 mg or                                        Nine randomized
                                                                                    placebo (vehicle)                                        patients did not
                        Double blind                            100 patients any                           vasospasm: incidence was
                                           9 neurosurgical                         injected at the time                                   receive treatment in
  Findlay et al.          placebo-                               WFNS grade                                 similar between groups.
                                           centers in North                            of aneurysm                                        the operating room.          84
      1995               controlled                             within 72 hours                             There was a trend toward
                                              America                                 clipping in the                                      All patients were
                        randomized                                 of SAH.                                       lesser degrees of
                                                                                   basal subarachnoid                                       treated with oral
                                                                                                           angiographic vasospasm in
                                                                                          cisterns                                             nimodipine
                                                                                                                  the rt-PA group
                                                                                   Coil embolization                At 6 months
                                                                                       + intrathecal       Symptomatic vasospasm:
                                                                 110 patients      urokinase infusion      9.4% urokinase vs. 28.1%        No side effects
                        Prospective                             Hunt and Hess       (cisterna magna)            no urokinase group           attributed to
  Hamada et al.                              2 university
                        randomized                                grade I-IV         for 24 hours vs.                (p=0.012).               urokinase.               86
     2003                                  centers in Japan
                         controlled                             within 24 hours    coil embolization.          Favorable outcome           Mortality similar
                                                                    of SAH            Evaluation of          (GOS): occurred more          between groups
                                                                                      outcomes was          often in urokinase group
                                                                                          blinded                    (p=0.036)
                                                                 166 patients       pTBA involving                                       pTBA reduced need
                                                                Fisher grade III       A1, M1, P1,                                       for subsequent TBA
                                                                                                           Incidence of DID and poor
                        Prospective                             within 72 hours    supraclinoid ICA,                                     to treat DID by 50%
Zwienenberg-Lee                                                                                              outcome similar among
                        randomized        Multi-center trial         of SAH        basilar artery, and                                         (p<0.05).               90
  et al. 2007                                                                                               groups (p=0.17 and 0.46
                         controlled                                (following           dominant                                         3 patients died from
                                                                   aneurysm        intradural VA vs.                                     vessel rupture during
                                                                   treatment)           no pTBA                                                  pTBA
                                                                                                                  At 6 months
                                                                                                                                            All patients were
                                                                                                               Favorable outcome
                                                                                         ++                                                   treated with
                                                                                    Mg 20 mmol                (GOS): similar among
                        Double blind          Regional            60 patients                                                                 intravenous
                                                                                      bolus + 80                    groups.
                          placebo-          neurosurgical       WFNS grade I-                                                               nimodipine. No
Wong et al. 2006                                                                   mmol/day or saline             Incidence of                                        129
                         controlled        center in Hong        IV within 48                                                                 difference in
                                                                                    infusion for 14        symptomatic vasospasm:
                      randomized pilot          Kong            hours of SAH                                                              functional outcomes
                                                                                         days                  43% saline vs. 23%
                                                                                                                                         (BI, NIHSS) between
                                                                                                            treatment group (p=0.06)
                                                                                                           Incidence of TCD-defined
                                                                                                                (MFV>120cm/s) and        Incidence of DID and
                                                                                                                  severe vasospasm        mortality decreased
                      Phase II, double         Single                                                       (MFV>200cm/s) reduced          by 83% (p<0.001)
                                                                  80 patients      Pravastatin 40 mg
                           blind,          neurosurgical                                                      by 32% (p=0.006) and        and 75% (p=0.037),
Tseng et al. 2005                                               within 72 hours    po vs. placebo for                                                                 139
                        randomized         department in                                                            42% (p=0.044),          respectively, in
                                                                    of SAH              14 days
                         controlled       United Kingdom                                                           respectively with       pravastatin group
                                                                                                               pravastatin treatment.         (secondary
                                                                                                                  Duration of severe           endpoints)
                                                                                                             vasospasm shortened by
                                                                                                                  0.8 days (p=0.068)
                                                                                                                 Clinical vasospasm
                                                                                                                 reduced (p<0.05) in
                                                                                   Simvastatin 80 mg           treatment (5 of 19) vs.       No significant
                                                                                   po vs. placebo for       placebo group (12 of 20).        differences in
                                                                  39 patients
                      Pilot randomized    Single center trial                           14 days.             Plasma von Willebrand        laboratory-defined
Lynch et al. 2005                                               within 48 hours                                                                                       140
                          controlled       in United States                           Investigators              factor and S100beta        transaminitis or
                                                                    of SAH
                                                                                       blinded to             decreased 3 to 10 days       myositis between
                                                                                    treatment group.           after SAH (P<0.05) in             groups
                                                                                                                treatment vs. placebo
                                                                                                                      On day 92
                                                                                                                  Moderate to severe
                                                                                                             angiographic vasospasm
                                                                                     Clazosentan                                           Clazosentan was
                                                                                                            significantly reduced in a
                        Randomized          Neurosurgical                             1mg/hour,                                           associated with an
                                                                 413 patients                                dose-dependent fashion
Macdonald et al.        double blind       centers in North                        5mg/hour, and 15                                      increased incidence
                                                                within 56 hours                              from 66% in placebo to                                   156
    2007                  placebo            America and                             mg/hour vs.                                            of pulmonary
                                                                    of SAH                                        36% in 15mg/hour
                         controlled            Europe                               placebo for 14                                       edema,
 ARDS, and
                                                                                                                 Clazosentan group.
                                                                                         days                                                hypotension
                                                                                                                      At 3 months
                                                                                                             No significant effect on
                                                                                                                    outcome (mRS)
                                                                                                                      At one year
                                                                                                            TCD-defined vasospasm
                                                                                                            more common in placebo
                        Randomized                                117 patients                                group (64.9% vs. 73%,         Patients in the
                                                                                   Enoxaparin 20mg
                        double blind         Single center      Grade I-III Hunt                               p=0.002). DID: 8.8%       placebo group had a
Wurm et al. 2004                                                                   sc vs. placebo for                                                                 157
                          placebo          study in Austria     and Hess within                                enoxaparin vs. 66.7%       worse Neurologic
                                                                                        21 days
                         controlled                             72 hours of SAH                             placebo group (p<0.001).     status on admission
                                                                                                               Cerebral infarction:
                                                                                                           3.5% treatment vs. 28.3%
                                                                                                            placebo group (p<0.001)
                                                                                                                      On day 81
                                                                                   NPRI placed in the                Angiographic
                                                                                    basal cisterns vs.         vasospasm: (primary
                                                                32 patients Hunt
                                                                                    wash out of basal      endpoint) 73% placebo vs.
                        Randomized                               and Hess grade
                                                                                    cisterns without             7% treatment group.
                       double blind,        Single center       III-IV within 48                                                         NPRI were tolerated
Barth et al. 2007                                                                        NPRI.               More favorable outcome                                   160
                      controlled phase         study            hours (following                                                               well
                                                                                      Angiography             (mRS and NIHSS) was
                             II                                     aneurysm
                                                                                       performed                seen in the treatment
                                                                                   preoperatively and            group. Death: 38%
                                                                                       on day 81           placebo vs. 6% treatment
                                                                                                                   group (p=0.042)

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