Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke
BACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke. METHODS: DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation, within 18 hours of onset of symptoms, in a multicenter, randomized, single-blind, dose-finding, controlled safety trial, consisting of 3 parts: 12 doses of 25, 50, and 100 mg/kg DCLHb over 72 hours. RESULTS: DCLHb caused a rapid rise in mean arterial blood pressure. The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment. Two patients in the 100 mg/kg group had adverse events that were possibly drug related: one suffered fatal brain and pulmonary edema, the other transient renal and pancreatic insufficiency. Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb (OR, 4.0; CI, 1.4 to 12.0) were independent predictors of a worse outcome (Rankin Scale score of 3 to 6) at 3 months. CONCLUSIONS: Outcome scale scores were worse in the DCLHb group, and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients. We recommend that additional safety studies be performed, preferably with a second generation, genetically engineered hemoglobin.
|Keywords||Acute Disease, Aged, Aged, 80 and over, Aspirin/administration & dosage/adverse effects/*analogs & derivatives, Blood Pressure, Blood Substitutes/*administration & dosage/adverse effects, Brain Ischemia/*drug therapy, Cerebrovascular Disorders/*drug therapy, Female, Hemoglobins/*administration & dosage/adverse effects, Humans, Male, Middle Aged, Research Support, Non-U.S. Gov't, Single-Blind Method, Treatment Outcome|
Saxena, R., Wijnhoud, A.D., Carton, H., Hacke, W., Kaste, M., Przybelski, R.J., … Koudstaal, P.J.. (1999). Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke. Stroke, 30(5), 993–996. Retrieved from http://hdl.handle.net/1765/9089