BY ED SUSMAN
HOUSTON—Treatment with a blood-clotting factor guided by CT angiography (CTA) failed to show that it could reduce expansion of intracerebral hemorrhage (ICH) in acute stroke patients, researchers reported here Friday at the 2017 International Stroke Conference sponsored by the American Heart Association/American Stroke Association.
The investigators wanted to determine if CTA-defined "spot signs" — tiny, enhancing foci within acute hematomas — could identify a subgroup of patients at increased risk for ICH expansion who may benefit from hemostatic therapy with recombinant factor VIIa.
"We saw no significant effect of recombinant factor VIIa on 24-hour ICH volume or 24-hour total volume, after adjusting for baseline ICH volume and onset to needle time," said David Gladstone MD, PhD, associate professor of medicine at the University of Toronto/Sunnybrook Research Institute.
At baseline, the blood volume in the lesions identified by the so-called spot sign on CTA and treated with factor VIIa was 16 mL. After 24 hours, that pool of blood had expanded to 22 mL compared to patients identified with the spot sign and not treated, whose pool of blood in the brain at baseline was 20 ml and that expanded to 29 mL (p=0.9), Dr. Gladstone reported in his presentation.
The total volume of the hemorrhage was 24 mL at baseline, and that rose to 26 mL at 24 hours in the patients treated with factor VIIa; in the patients given placebo, the total median volume rose from 25 mL to 31 mL (p=0.9), which was not significant, he said.
About 41 percent of the patients given factor VIIa showed a 6 mL increase or a 33 percent increase in ICH compared with 43 percent of the patients on placebo (p=0.83), the researchers reported.
Dr. Gladstone presented the data from SPOTLIGHT (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy) study, which was conducted in Canada. The study pooled its results with a similar study, called the STOP-IT (Spot Sign for Predicting and Treating ICH Growth) trial, conducted in the United States.
Matthew Flaherty, MD, associate professor of neurology at the University of Cincinnati, who led the STOP-IT study, said the trial took a long time to recruit just the 69 patients who were found to be spot sign-positive and the three patients who were observed as spot sign-negative, meaning the focal enhancing spot on the CT was not seen. The researchers then assigned 32 of the spot sign-positives to treatment with factor VIIa; 37 patients with the positive sign — believed to indicate active bleeding — were not given the clotting factor.
The recruitment took six years, mainly due to difficulty in meeting the strict inclusion and exclusion criteria. and in getting patients to the hospital and from the hospital to start intravenous treatment in a reasonable amount of time.
Dr. Gladstone said the theory was that by using the spot sign to identify patients with ICH whose hemorrhages were still expanding, and by treating them with the clotting factor — approved currently only for hemophilia patients — they could reduce the size of the hemorrhage and the outcomes of the patients.
But the 90-day outcomes in the study showed no significant differences on the modified Rankin Scale score (p=0.96) between the groups with spot signs.
"We are going to think very carefully about how best to interpret the results, but these are the first randomized data attempting this treatment in spot sign-positive patients. This data will help guide future research. We have learned a lot that will help us design the next studies," Dr. Gladstone said.
Commenting on the study, Bruce Ovbiagele, MD, FAAN, professor and chair of neurology at the Medical University of South Carolina in Charleston, said: "I think this trial has merit and should be pursued. In the SPOTLIGHT/STOP-IT studies, we have a devastating condition for which there is no treatment whatsoever and we have an imaging marker that is widely available. The only issue is in regard to timing. I endorse the efforts of trying to incorporate this into the pre-hospital treatment of stroke patients.
"I think this confirms our knowledge that this marker is valid," said Dr. Ovbiagele, who moderated the press briefing. "It shows we have to be faster in the way we treat people. I think there is value here."
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