The STICH trial: what does it tell us and where do we go from here?

Until the present, intracerebral hemorrhage (ICH) has been the stroke subtype that has defied attempts to find a scientifically proven effective therapy. Possible treatments of acute ICH include: (1) slowing or stopping of the bleeding during the first several hours after onset or (2) removal of the accumulated hematoma to prevent the mechanical complications of mass effect as well as the toxic effects of blood on the surrounding brain parenchyma. Critical care management of the complications of ICH is clearly important. The evolution of lesions and the pathophysiology of intracerebral hemorrhage, like that of ischemic stroke, are time-dependent,1,2 but only the recently published trials of Novo VII have tried to intervene during the first hours after onset of ICH.3,4 The recent publication of the Novo VII phase II trial also provides hope that an effective treatment for acute ICH is within reach. The STICH Trial represents an important milestone in the role of surgical treatment for ICH.5 The relative paucity of data from randomized trials has severely limited progress in the surgical treatment of ICH and has led to substantial variability in the management of ICH throughout the world. Dr Mendelow, collaborators, and the Medical Research Council (MRC) are to be congratulated for completing the largest ever randomized treatment trial of ICH. This trial adds substantially to what we know about surgical management of ICH and will have an impact on current treatment as well as design of future trials. The goal of the STICH Trial was to investigate the effectiveness of early surgery (within 24 hours of randomization) as compared with initial conservative medical treatment with later evacuation if deemed necessary by the treating neurosurgeon. The STICH Trial showed no significant difference in outcome between the early surgical and initial conservative management groups. Of the prespecified subgroups that were examined, patients with an ICH within a centimeter of the cortical surface showed a benefit for early surgery and there was a significant treatment interaction between treatment assignment and depth of the ICH from the cortical surface. However, statistical testing of this subgroup was not adjusted for the multiple subgroup comparisons as the investigators note. The STICH investigators concluded that “patients with spontaneous supratentorial ICH in neurosurgical units show no overall benefit for early surgery when compared with initial conservative management.” The design and conduct of the STICH Trial are keys to interpretation of the STICH Trial. Inclusion criteria for STICH included computed tomographic evidence of a spontaneous supratentorial ICH that had arisen within 72 hours, uncertainty concerning the benefits of either treatment by the treating neurosurgeon, and a recommendation for a minimum hematoma diameter of 2 cm and a Glasgow Coma Score of 5 or more. Exclusion criteria included ICHs likely caused by an aneurysm or an angiographically proven arteriovenous malformation, tumor, or trauma; cerebellar or brain stem ICH; and inability to perform surgery within 24 hours of randomization. An important characteristic of the care plan was that patients randomized initially to conservative management could undergo evacuation of the ICH if clinically indicated in the judgment of the treating physicians. This latter design feature reflects the clinical reality that ICH patients, on average, the most gravely ill of all stroke patients, frequently die despite the best efforts of physicians, nurses, and other health care personnel. In the face of marked deterioration and imminent death, holding to a course of medical management may be challenging. The surgical approach was left to the choice of the treating neurosurgeons. In 77% of cases, craniotomy was the surgical procedure and the remainder of cases had hematoma removal by burr hole, endoscopy, or stereotaxy in similar numbers. Thus, the STICH Trial is primarily a trial of craniotomy for ICH removal. Interestingly, there was a borderline statistical interaction (P 0.07) between surgical method and outcome. Timing of surgery in the STICH Trial, even in the “early surgery group,” was relatively long after onset of symptoms. The median time from onset to treatment for early surgery group was 30 hours (interquartile range, 16 to 49 hours); thus, this trial cannot speak to the effectiveness of surgery within