I'm sure many of you have read about the disappointing reviews of the performance of blood substitutes in recent trials. Specifically, the authors in a recent edition of the Journal of the American Medical Association (JAMA) agreed in a benefit for a synthetic blood product that wouldn't have infection or compatibility risks and would have a long shelf life. However, they felt clinical trials for the first generation of these products showed too high a risk.
In the JAMA article, published in the April 29, 2008 issue, Dr. Natanson and the other researchers sought to assess the safety of Hemoglobin-based blood substitutes in surgical, stroke and trauma patients. They did this through a meta-analysis of the clinical trials to date.
They looked at 70 trials. Thirteen met their criteria for randomized controlled trials. Two others were reported in the press, and another was from an FDA review.
Five different products were used in 16 trials on 3,711 patients. They reported a statistically significant risk of death with 164 deaths in the treated groups and 123 in the control groups. They reported 59 myocardial infarctions (MIs) in the treated groups versus 16 in the control groups. The risk wasn't restricted to any of the five products. They concluded, "Based on the available data, use of HBBSs is associated with a significantly increased death and MI."
In another article in the same edition of JAMA, Dean Fergusson, MHA, PhD, and Lauralyn McIntyre, MD, MSc, wrote the editorial "The Future of Clinical Trials Evaluating Blood Substitutes." In the editorial, hey discussed the risk of testing these products in human trials in the face of what they described as an adequate and safe blood supply. In their final paragraph they stated, "Given the safety of the blood supply, availability of blood products, and technologies to minimize transfusion, it does not seem prudent to study the use of Hemoglobin-Based Oxygen carriers in elective surgical populations."
Beyond the obvious disappointment that these products won't be in our ambulances soon, the current results jeopardize other studies that are due to begin.
In an article published at Bioworld.com, author Tiffany Turner discussed the studies to date with experts, along with what may be in the future. In her article, she described the progress made by Biopure with its Hemopure product. Currently working with the FDA to establish protocols for clinical trials, Biopure is also working with the U.S. Navy to develop Hemopure as a blood substitute for trauma patients. According to the article, the U.S. Department of Defense has allocated significant funding for the project.
The article indicated that Hemopure was approved for treatment of acutely anemic surgical patients. In it, Turner stated 460 patients received the product with Biopure noting no serious adverse affects.
Other types of products are promoted as blood replacements like HemoBio Tech's Hemo Tech, which is derived from bovine hemoglobin. They believe their product will avoid the toxicity pitfalls the Human Hemoglobin based products have faced.
So the disappointment is two-fold. The first disappointment is that the products aren't ready for us. The second is that the results may make it harder for clinical trials in the future. However, we have hope that lessons learned in the first-generation substitutes are already helping the second generation avoid the risks shown in the studies so far.