alphaalpha-crosslinked hemoglobin: was failure predicted by preclinical testing?
alphaalpha-crosslinked hemoglobin: was failure predicted by preclinical testing?
复制标题
αα交联血红蛋白：临床前测试是否预测失败？
DOI：
10.1159/000031200
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发表时间：
2000
期刊：
影响因子：
2.7
通讯作者：
Winslow,RM
中科院分区：
文献类型：
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作者：
Winslow,RM
1998年，巴克斯特医疗保健公司宣布放弃其产品二阿司匹林交联血红蛋白（DCLHb），这是第一个完成所有人体试验阶段的“血液替代品”。该公司宣布，在人类中进行的III期（关键）试验导致了一组患者的意外高存活率，这些患者作为在创伤环境中接受其产品的对照组。从1985年到1998年，在开发这一产品的过程中所花费的时间、精力和金钱无法量化。有传言称，这家大型医疗保健公司在这款产品上花费了超过5亿美元，更不用说美国陆军、美国国立卫生研究院和许多独立的大学科学家对同一产品的投资了。失望是深刻而深远的。虽然在发达国家，库存血液传播艾滋病毒的威胁几乎已经消失，但世界上大部分人口仍然面临血液短缺，这种产品及其后代可能有助于缓解这种情况。只有巴克斯特和美国食品药品监督管理局可能永远了解本产品开发历史的关键要素。然而，由于美国陆军决定将其版本的产品广泛提供给科学家，因此有大量的出版记录，由巴克斯特和独立科学家贡献。对这一记录的审查得出的结论是，没有单一的失败原因。然而，这表明ααHb引起的特征性血流动力学反应增加了血管阻力，可能消除了其作为红细胞替代品的潜力。当这个问题被克服时，克服这个限制的较新的解决方案应该在临床开发中表现得更好。
In 1998, Baxter Healthcare announced that it was abandoning its product, diaspirin–crosslinked hemoglobin (DCLHb), the first ‘blood substitute’ to complete all phases of human trials. The company announced that the phase III (pivotal) trials in humans had resulted in an unexpectedly high survival in a group of patients serving as controls for those who received their product in a trauma setting. It is not possible to quantitate the time, efforts and money that were expended in the course of developing this product, from 1985 to 1998. It is rumored that the giant healthcare company had expended more than a half billion dollars on this product, not to mention the investment in the same product by the US Army, the National Institutes of Health and many independent university–based scientists. The disappointment was profound and far–reaching. Although the threat of HIV transmission by banked blood has all but disappeared in the developed world, still the bulk of the world’s population faces blood shortages, which this product and its future generations might have helped alleviate. Only Baxter and the Food and Drug Administration may forever know key elements of the history of development of this product. However, because the US Army decided to make its version of the product widely available to scientists, there is a substantial published record, contributed to by both Baxter and independent scientists. Examination of this record leads to the conclusion that there is no single reason for failure. However, it shows that the characteristic hemodynamic response caused by ααHb increased vascular resistance, and probably eliminates its potential as a red cell substitute. Newer solutions that overcome this limitation should fare better in clinical development when this problem is overcome.