Abstract | BACKGROUND: METHODS AND RESULTS: Double-blind, parallel group, placebo-controlled trial of a single 24-hour intravenous infusion of trafermin. Patients having onset of stroke symptoms within 6 h and a baseline score of >/=7 on the NIH Stroke Scale (>/=2 motor) were randomized to receive 5 or 10 mg of trafermin or placebo intravenously infused over 24 h. The primary efficacy outcome was a categorized combination of the Barthel and Rankin scales assessed at 90 days. A total of 286 patients had been enrolled at 55 sites in 11 countries when the sponsor directed that enrollment be stopped because an interim analysis of efficacy data predicted too small a chance of demonstrating a statistically significant benefit after recruitment of the planned 900 patients. The 5-mg group showed a slight but nonsignificant advantage over placebo (OR 1.2, 95% CI 0.72-2.00, p = 0.48); the 10-mg group showed a nonsignificant disadvantage (OR 0.74, 95% CI 0.44-1.22, p = 0.24). Mortality rates at 90 days were 17% in the 5-mg group, 24% in the 10-mg group and 18% in the placebo group. Treatment with trafermin was associated with an increased leukocytosis and a decrease in blood pressure: mean decrease in systolic blood pressure from baseline was 19 mm Hg in the 5-mg group, 22 mm Hg in the 10-mg group and 8 mm Hg in the placebo group. In a post hoc subgroup analysis, patients in the 5-mg group treated more than 5 h after the onset of symptoms showed an apparent advantage over placebo (OR 2.1, 95% CI 1.00-4.41, p = 0.044; after age adjustment: OR 1.9, 95% CI 0.91-4.13, p = 0.08). CONCLUSIONS: With the proper treatment regimen, trafermin can likely be given safely to stroke patients. The 5-mg dose showed a trend toward a treatment advantage. The ideal time window for this agent may exceed 5 h. This may open new avenues for acute stroke therapy, aiming at enhancing recovery mechanisms rather than immediate neuroprotection.
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Authors | Julien Bogousslavsky, Stephen J Victor, Eliseo O Salinas, Allan Pallay, Geoffrey A Donnan, Cesare Fieschi, Markku Kaste, Jean-Marc M Orgogozo, Angel Chamorro, Anne Desmet, European-Australian Fiblast (Trafermin) in Acute Stroke Group |
Journal | Cerebrovascular diseases (Basel, Switzerland)
(Cerebrovasc Dis)
Vol. 14
Issue 3-4
Pg. 239-51
( 2002)
ISSN: 1015-9770 [Print] Switzerland |
PMID | 12403958
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
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Copyright | Copyright 2002 S. Karger AG, Basel |
Chemical References |
- Peptide Fragments
- trafermin
- Fibroblast Growth Factors
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Topics |
- Dose-Response Relationship, Drug
- Double-Blind Method
- Drug Administration Schedule
- Fibroblast Growth Factors
(administration & dosage, adverse effects, therapeutic use)
- Humans
- Infusions, Intravenous
- Peptide Fragments
(administration & dosage, adverse effects, therapeutic use)
- Safety
- Stroke
(drug therapy, physiopathology)
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