LONDON, United Kingdom — Despite showing nonsignificant results on the primary endpoint, the second Surgical Trial in Lobar Intracerebral Hemorrhage (STICH II trial) may still have identified a small population with spontaneous intracerebral hemorrhage (ICH) who may benefit from early surgery.
In the trial, early surgery did not increase the rate of death or disability at 6 months and suggested a small survival advantage for patients with ICH who do not have intraventricular hemorrhage.
Presenting the study, Professor David Mendelow, FRCS, Newcastle University, Newcastle Upon Tyne United Kingdom, explained that ICH is not a homogenous condition.
"At present, we generally operate on about 20% of patients. These are the ones with a large hemorrhage who are deteriorating before our eyes," he said. "This involves a craniotomy and removing the clot, but if the patient is fully conscious and only has a small hematoma, we normally don't operate. In this trial we were focusing on patients in the middle — those with lobar hematomas for whom it is uncertain whether surgery would be beneficial."
"Our results add another 2-3% or so of patients who we think would benefit from early surgery," he added. "This was already a selected group as we had ruled out the patients with the worst prognosis. In the population studied the ones with a poorer prognosis (GCS [Glasgow Coma Scale score] 8-15) tended to do better with surgery rather than watching and waiting. There was less benefit in the patients with a better prognostic score."
Commenting on the STICH II results for Medscape Medical News, Professor Martin Brown, University College London, United Kingdom, said, "The benefits are not immediately obvious. I think it is a little too early to know if it will change clinical practice. I need to examine the results more thoroughly. It supports current practice of making a decision on whether to operate or not on an individual patient basis, and surgery will still be limited to a small population, usually the younger, sicker patients."
Results of STICH II were presented here at the European Stroke Conference (ESC) on May 29 and published simultaneously online in The Lancet.
Worse With Surgery
Professor Mendelow noted that previous trials have suggested that patients with deep-seated bleeding or with intraventricular hemorrhage and hydrocephalus do worse with surgery, whereas those with superficial lobar hematomas without intraventricular hemorrhage tend to do better. STICH II was done to confirm a benefit of surgery in the latter group.
The trial involved 601 patients who had a spontaneous lobar ICH on computed tomography (1 cm or less from the cortical surface of the brain) with a volume of 10 to 100 mL, were within 48 hours of ictus, and had a best motor score on the GCS of 5 or 6, and a best eye score of 2 or more. They were randomly assigned to early surgery or conservative treatment.
The primary outcome was a prognosis-based favorable or unfavorable outcome as defined by the score on the Extended Glasgow Outcome Scale at 6 months. This was calculated by answers to 14 questions sent by mail to patients or their relatives.
There was quite a large crossover in the conservative group, with 21% of these patients ending up having surgery, mostly because of deterioration. Professor Mendelow noted that "these are the ones with the worst prognosis when surgeons are compelled to operate."
The intention-to-treat primary analysis showed a small but nonsignificant increase in the number of patients having a favorable outcome at 6 months in the early surgery group. There was also a suggestion of a reduction in mortality, but this finding was also nonsignificant.
Table. STICH-II: 6-Month Results
|Outcome||Early Surgery (%)||Conservative Treatment (%)||Odds Ratio (95% Confidence Interval)||P Value|
|Favorable outcome||41||38||0.86 (0.62 - 1.20)||.367|
|Death||18||24||0.71 (0.48 - 1.06)||.095|
Professor Mendelow said that the difference between the 2 groups was less than expected. "A benefit of 4% is not really enough to change practice. We were hoping to see a 12% difference," he commented.
And he suggested that they were unlucky with the mortality result as deaths were significantly lower in the surgery group at 30 and 90 days but not at 6 months — the time of the primary endpoint.
A proportional odds model, which is sensitive to differences across the outcome scale rather than just classifying patients as having a "favorable" or "unfavorable" outcome, also suggested a benefit with surgery, with a lower P value than the primary outcome (P = .075).
Because good and poor prognosis was used as part of the primary endpoint, the effect of surgery was examined in the 2 prognostic groups separately. This showed that patients with a poor prognosis did better with early surgery, whereas those with a good prognosis did not.
Professor Mendelow commented: "Our results suggest that the poor prognosis patients (GCS of 9-12) are better off with early surgery. But if they fall into the good prognosis group, the best option is to just watch them, and only operate in those that later deteriorate."
During the discussion, it was pointed out that the trial seemed underpowered, and it was suggested that including individual-patient data from similar patients in STICH I might make a difference. Professor Mendelow replied, "Yes, we were underpowered, and even with the similar patients from STICH I it does not quite reach statistical significance sadly."
In a Comment accompanying the Lancet publication, Oliver P. Gautschi and Karl Schaller, University of Geneva, Switzerland, stress that continuing interdisciplinary research is of paramount importance for further development of evidence-based treatment guidelines for patients with ICH.
Noting that, "So far, the best evidence available is derived from STICH II, although overall the evidence is insufficient," they add that further results from 2 trials using minimally invasive procedures — CLEAR III (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III) and MISTIE III (Minimally Invasive Surgery plus rt-PA for ICH Evacuation III) — are eagerly awaited.
STICH II was funded by the UK Medical Research Council.
European Stroke Conference (ESC). Presented May 29, 2013.
Medscape Medical News © 2013 WebMD, LLC
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