Drug combo doesn’t stem VWD postpartum bleeding, trial finds

Adding Cyklokapron (tranexamic acid) to Vonvendi (recombinant von Willebrand factor) does not appear to reduce blood loss following childbirth for women with von Willebrand disease (VWD), according to results from a small clinical trial.

“[Cyklokapron] plus [Vonvendi] is feasible and safe in type 1 VWD, but in this small pilot study, was not associated with a reduction in [postpartum hemorrhage] compared to [Vonvendi] alone,” the researchers wrote.

They detailed their findings in the study, “Impact of Tranexamic Acid on Postpartum Hemorrhage in Type 1 von Willebrand Disease Treated with Recombinant VWF,” published in Blood Advances. Takeda Pharmaceuticals, the company that markets Vonvendi, funded the work.

VWD is a bleeding disorder caused by deficits in a clotting protein called von Willebrand factor (VWF), which leads to symptoms like heavy and prolonged bleeding. Postpartum hemorrhage (severe blood loss following childbirth) can be a major health risk for women with VWD.

Vonvendi is a recombinant, or lab-made, version of the VWF protein administered by injection into the bloodstream. It’s approved in the U.S. for use as both a prophylactic (preventive) and on-demand treatment for adults with VWD. Cyklokapron is an antifibrinolytic therapy, a medication that promotes blood clotting by blocking molecular mechanisms that normally cause clots to break down.

Data on combo treatment lacking

A Phase 3 clinical trial called WOMAN (NCT00872469) tested Cyklokapron against a placebo in more than 20,000 women giving birth, and results showed that Cyklokapron significantly reduced the risk of death from postpartum hemorrhage. Based on these data, the therapy has become a mainstay for managing bleeding in childbirth. In women with VWD, it’s often used in combination with VWF replacement therapies such as Vonvendi.

“While often used in clinical practice, there is limited randomized trial data regarding the efficacy and safety of the combination of [Cyklokapron] with VWF concentrate to optimize hemostasis in women with VWD at delivery,” the researchers wrote.

The team, led by scientists at the University of Pittsburgh Medical Center, conducted a pilot clinical trial to gather more data.

The study, dubbed VWD-WOMAN (NCT04344860), enrolled 20 pregnant women with VWD. The women had a mean age of 29, and most (90%) were white. All of them were given three injections of Vonvendi — the first at the time of delivery, and the next two on the first and second day after birth. Half of the patients were also given 1 g of Cyklokapron within the first three hours of delivery.

The main goal was to see if the amount of blood lost at childbirth would significantly differ in women given Cyklokapron.

Results, however, showed no significant difference in postpartum blood loss between patients who did or did not receive the antifibrinolytic therapy. In fact, the median amount of blood lost was a bit higher among patients given Cyklokapron.

Four of the women — three of whom received Cyklokapron and one who did not — experienced postpartum hemorrhage, defined as a loss of more than one liter of blood.

Safety data from the study revealed no serious side effects, clotting problems, or allergic reactions.

This study was open to women with all types of VWD, but all of the women who participated had VWD type 1, which is marked by low but detectable levels of the VWF protein. Because the study only included patients with VWD type 1, the researchers said it’s uncertain whether the results apply to other types of the disease. They also stressed that it was a small, pilot trial, and the results should be considered exploratory.

“While the study provides encouraging data on the safety of conducting clinical trials in pregnant women with VWD, as well as the safety of combining [Vonvendi and Cyklokapron] in postpartum management in women with type 1 VWD, the limitations underscore the necessity for larger, more diverse studies including other VWD subtypes,” the scientists wrote.