Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke.
OBJECTIVE
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.
Saxena
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Department of Neurology, University Hospital Dijkzigt, Rotterdam, the Netherlands. Koudstaal@neur.azr.nl
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D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D001794:Blood Pressure; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000009:adverse effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D005260:Female; D006454:Hemoglobins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D016896:Treatment Outcome
D001802:Blood Substitutes; D006454:Hemoglobins; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin