The blood thinning effects of dabigatran (Pradaxa) can be quickly and reliably reversed by giving idarucizumab (Praxbind) for people who have urgent uncontrolled bleeding, according to final results of a large 39-country study financed by the manufacturer, Germany’s Boehringer Ingelheim.
Idarucizumab appeared to reverse the action of the blood thinner – based on clotting times – in nearly all 503 volunteers within four hours, according to the new findings, reported Tuesday at the International Society on Thrombosis and Haemostasis Congress in Berlin and published online by the New England Journal of Medicine.
“It was like 99 percent,” chief author Dr. Charles Pollack Jr. of Thomas Jefferson University in Philadelphia told Reuters Health in a phone interview from Germany.
“Reversal was rapid and occurred independently of age, sex, renal function and dabigatran concentration at baseline,” he and his team reported.
In 2015, the U.S. Food and Drug Administration gave accelerated approved to idarucizumab for emergency situations to stop dangerous bleeding among dabigatran recipients.
The latest data from the RE-VERSE AD study looked at 301 people on dabigatran who had uncontrolled bleeding, mostly through gastrointestinal bleeding or an intracranial hemorrhage, and 202 patients also on the drug who were about to undergo an urgent procedure that could not be delayed for eight hours.
In the first group, the median time to the cessation of bleeding was 2.5 hours after 5 grams of intravenous idarucizumab.
In the group getting unexpected surgery or some other procedure, the procedure typically started 1.6 hours after administration of the drug, and in 93.4 percent of the cases, periprocedural hemostasis was considered to be normal. It was judged mildly abnormal in 5.1 percent of the cases and moderately abnormal in 1.5 percent.
“Idarucizumab enabled surgery or an intervention in 197 of 202 patients,” the Pollack team reported. The treatment costs about $3,000 to $3,500 in the United States, the team said. Mortality rates were virtually identical in both groups – just under 19 percent.
When the researchers checked the volunteers at the 90-day mark, 6.3 percent of the group that had uncontrolled bleeding had suffered a thrombotic event versus 7.4 percent in the unplanned procedure group. There were no control groups. Effectiveness was measured by diluted thrombin time or ecarin clotting time. Nine volunteers (1.8 percent) received additional idarucizumab.
There were three cases of hypersensitivity to the drug, Over all, serious adverse events were seen at a rate of 23.3 percent in the uncontrolled bleeding group and 25.2 percent in the urgent surgery group, but in most cases those events seemed to be related to the problem that brought them to the hospital in the first place, or a coexisting condition.
“The safety of idarucizumab observed in this study supports its urgent use even if patients later prove to have had little or no circulating dabigatran,” the team concluded.
“Even in patients with severe renal insufficiency, the effects are gone within a day or two. From that point forward it’s fine to put them back on dabigatran,” Dr. Pollack said.
Clinically, the outcomes were more complicated. In the uncontrolled bleeding group, it was not possible to pinpoint when bleeding stopped in 98 cases of intracranial bleeding, or in 67 other patients.
“We know that dabigatran was reversed, we just can’t say when the bleeding stopped,” said Dr. Pollack.
The researchers were able to confirm bleeding cessation within 24 hours in 134 other patients. In the urgent surgery group, many patients received blood products. Interim results involving the first 123 patients were released in April 2016.