Drug makers have been trying to find an alternative to protamine, which is thought to have a negative effect on blood pressure which has been linked to increased mortality in some patients. The drug has also been found to depress heart function, activate certain immune responses and lead to pulmonary hypertension.
In response, Canadian firm Ibex developed heparinase I, a compound naturally produced by flavobacterium heparinum. This bacterium enzyme deactivates heparin, which prevents clots from forming in the heart-lung machine during surgery, through a different mechanism to protamine.
However, the current phase trial being carried out at 47 sites in the US, Canada and Germany was stopped early on because patients receiving heparinase I had higher occurrences of negative side effects, such as bleeding and infections.
Since protamine’s launched in the early 1960s, the FDA has not approved an effective alternative that will reverse the properties of heparin.
“The results of this study clearly demonstrate that more research is needed to develop a protamine alternative,” said Mark Newman, chairman of anesthesiology at Duke. “As in the use of all medications, there must be judgments made about the risks and benefits. Because of the limited alternatives available to us at this point, the benefits of protamine still exceed the risks, at least until we find something better.”