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Study: NovoSeven Coagulation Factor VIIa Shows Reduction in Hematoma Growth
The preliminary results of this trial were initially presented at the Fifth World Stroke Congress in Vancouver, B.C. in June 2004, and most recently at the International Stroke Conference in New Orleans, LA in February 2005.
"One of the strongest predictors of mortality and morbidity in ICH patients is hematoma volume and with the administration of NovoSeven hematoma growth was significantly limited," said Dr. Stephan Mayer, associate professor and director, Neurological Intensive Care Unit, Columbia University Medical Center and lead investigator of the study. "The current medical and surgical treatment options for ICH are not effective. Thirty-five to fifty percent of patients die within one month and if they survive, they are living with serious neurological deficits. The current data suggest a possible change in our paradigm for the treatment of ICH."
The trial results showed that treatment of ICH with rFVIIa within four hours of symptom onset reduced mortality and improved three-month clinical outcome, along with the reduction in hematoma growth, despite a greater frequency of thromboembolic events.
The trial included 399 patients, all diagnosed by Computed Tomography Imaging (CT Scan) within 3 hours of ICH onset. Patients were randomly assigned to receive placebo (N=96), 40 (N=108), 80 (N=92), or 160 (N=103) micrograms/kg doses of rFVIIa within one hour of the baseline scan.
The primary endpoint of the study was to determine if recombinant activated Factor VII (rFVIIa) could reduce hematoma growth after ICH. The primary outcome measure was the percent change in ICH volume at 24 hours. Clinical outcomes were assessed at 90 days.
Key Findings Reported in the NEJM article include:
* Primary endpoint: reduction in percent hematoma growth
-- ICH volume growth in the 40, 80, and 160 micrograms/kg treatment groups (P=0.01, rFVIIa vs. placebo) was 16%, 14%, and 11% respectively (corresponding to a relative reduction of 45%, 52% and 62%)(2) compared to 29% in the placebo treatment group.
* Secondary endpoint: Significant improvement in neurological and clinical
outcome and decreased mortality and morbidity
-- Mortality was reduced by 38% for rFVIIa-treated patients compared to placebo-treated patients (P=0.02).
-- 69% of placebo-treated patients died or were severely disabled (modified Rankin Scale (mRS) score 4-6), compared to 53% of the rFVIIa-treated patients (P=0.004).
-- Receiving rFVIIa more than doubled a patient's chances of improving one level on the mRS.
-- This represents a 16% absolute reduction in the risk of death or severe disability at three months according to the mRS.
* Safety endpoint: The overall frequency of fatal or disabling thromboembolic serious adverse events did not differ between the rFVIIa (2%) and the placebo (2%) groups. However, arterial thromboembolic serious adverse events occurred statistically significantly more frequently with rFVIIa treatment (5%) than with placebo (0%), manifesting in the form of myocardial ischemic events and cerebral infarction. The majority of patients recovered from these complications.
"We are very encouraged by the positive data from this study for NovoSeven(R) in the treatment of ICH," said Michael Shalmi, M.D., MBA, vice president, biopharmaceuticals, Novo Nordisk Inc. "Patients suffering an ICH have not had any well documented treatment options available. These results fuel our desire to further study the use of NovoSeven in ICH and other critical bleeding indications."
NovoSeven Coagulation Factor VIIa (Recombinant) is indicated for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX. NovoSeven is the only recombinant FVIIa for effective, reliable treatment of bleeding episodes in these patients. Its unique mechanism of action induces hemostasis independently of FVIII and FIX.
Intracerebral Hemorrhage (ICH) is the deadliest and most disabling type of stroke. ICH is bleeding within the brain which can start spontaneously rather than from external factors such as head trauma. During ICH, blood accumulates in the brain, creating a reservoir of blood called a hematoma. Larger hematomas are more likely to create permanent brain damage which can cause severe permanent physical and mental disability, and in many cases death. Fifteen percent of all stroke victims will be diagnosed with ICH in the US. Mortality occurs in 35-52% of these patients within one month, and less than 20% of the survivors are likely to become functionally independent.
Source: Novo Nordisk