By AMERICAN HEART ASSOCIATION NEWS

0224-ISC-hemorrhage_WP

HOUSTON — Doctors had hoped a drug used to stop bleeding could be a potential emergency treatment for brain hemorrhages.

Now, two parallel trials in Canada and the United States show that recombinant activated coagulation factor VII did not help high-risk patients with intracerebral hemorrhage, the most severe type of stroke that’s caused by bleeding in the brain.

Canada’s SPOTLIGHT trial and the American STOP-IT trial are the first randomized studies to test the therapy on high-risk ICH patients — those with a “spot sign” on CT angiography images who are most likely to benefit from treatment.

The spot sign appears as a bright dot inside a hemorrhage. Doctors think a spot sign shows expanded bleeding, which usually leads to rapid worsening.

“There is a desperate need to develop therapies for ICH that can save lives and reduce disability,” said the Canadian trial’s lead investigator David Gladstone, M.D., Ph.D., of the University of Toronto department of medicine and Sunnybrook Research Institute. “We hoped to see a magnified benefit of factor VII to stop bleeding, but the neutral trial results reminded us again just how difficult this condition is to treat.”

Gladstone presented the findings Friday at the American Stroke Association’s International Stroke Conference in Houston.

Steven Greenberg, M.D., Ph.D., co-chair of the ICH guidelines committee for the American Heart Association, said the findings won’t change ICH care management or guidelines.

“The findings clearly won’t be used to support factor VII as a treatment for brain hemorrhages,” said Greenberg, director of the Hemorrhagic Stroke Research Program at Massachusetts General Hospital in Boston, who wasn’t involved in the study. “The question is whether they add to data for spot sign usefulness in picking out patients at risk for expansion.”

They do, said STOP-IT lead investigator Matthew Flaherty, M.D., of the University of Cincinnati department of neurology. Both trials reaffirm the spot sign’s value as an important predictor of ICH expansion and prognosis, he said.

Roughly 10 percent of the 795,000 annual strokes in the United States are ICH, which has no proven emergency treatment and high death rates. Studies show that up to 40 percent of ICH patients suffer significant increases in bleeding. Current treatments include blood pressure management, supportive care and surgery in some cases.

Previous studies found that factor VII helped reduce bleeding in ICH patients, but didn’t provide a clinical benefit. The hemostatic drug is used to treat patients with hemophilia and a bleeding disorder called congenital factor VII deficiency, and is used off-label for other bleeding conditions.

The SPOTLIGHT/STOP-IT researchers wanted to see if factor VII would benefit patients deemed to be at higher risk of hematoma expansion through CT angiography spot sign. Doctors are increasingly using CT angiography for rapid diagnosis of stroke types.

The researchers recruited 69 ICH patients with a spot sign and 73 without a spot sign at 26 hospitals from 2010 to 2016.

Patients with a spot sign were randomly given an injection of the drug or a placebo within 6.5 hours of stroke symptom onset, with outcomes measured at 24 hours and 90 days. Lower-risk patients without a spot sign weren’t treated.

In patients with a spot sign, there was no significant difference between the treatment and placebo groups in terms of final hemorrhage volumes at 24 hours or clinical outcomes at three months, by which time about 20 percent of patients had died and 14 percent were severely disabled.

Among patients without a spot sign, 6 percent died and two-thirds had recovered functional independence by three months.

Challenging patient recruitment led to a small sample size, which prompted researchers to pool their data for analysis but limited “firm conclusions,” Gladstone said.

In addition, most patients were treated more than three hours after stroke onset, which is too late since most expansion already occurred, he said.

“We still believe hemostatic therapy holds promise, but we need to treat patients much faster – within 90 minutes of stroke onset,” Gladstone said at ISC. “We want to see treatment move out of the hospital setting and into the ambulance. Brain hemorrhages enlarge quickly and every minute counts.”