Background: Although hemophilia A mainly affects males, carriers (defined as females with hemophilia A, as well as symptomatic or asymptomatic hemophilia A carriers) are at risk of excessive bleeding, particularly during trauma or during surgical procedures. Clinical trials have focused on male patients with severe disease, and data for females are limited. Improved, evidence-based treatment guidelines for management of hemophilia A carriers are required.
Objectives and design: The NuDIMENSION study is a phase IV, prospective, open-label, single-arm study that will evaluate the perioperative efficacy and safety of simoctocog alfa (Nuwiq®), a recombinant factor VIII (FVIII), in women/girls with hemophilia A undergoing major surgery. The study will be conducted at approximately 15 centers worldwide. Women/girls aged ⩾12 years, with mild or moderate hemophilia A (residual FVIII activity (FVIII:C) ⩾1% to <40%) and with no current/past FVIII inhibitors are eligible. All patients must be scheduled to undergo a major surgical procedure during which simoctocog alfa will be administered.
Methods and analysis: The primary endpoint is overall perioperative hemostatic efficacy ("success" or "failure") of simoctocog alfa. Hemostatic efficacy will be assessed at the end of surgery and at the end of the postoperative period (i.e., completion of wound healing), with overall adjudication by an Independent Data Monitoring Committee. Safety endpoints will include the incidences of thrombotic events and FVIII inhibitor development. The aim is to recruit 28 patients to achieve 26 evaluable surgeries.
Ethics: Ethical approval will be received from institutional review boards/independent ethics committees, and the study will be conducted in compliance with the Declaration of Helsinki.
Discussion: Data from NuDIMENSION will generate much-needed evidence on surgical management of women/girls with hemophilia A, which will help to enable the development of treatment guidelines specific for such patients.
Trial registration: CT EU 2022-502061-17-00; NCT05936580.
Keywords: carrier; factor VIII; female; hemophilia A; simoctocog alfa; surgery; women.
Design of an international study (NuDIMENSION) to examine the use of a factor VIII therapy during surgery in female hemophilia A patients Hemophilia A is an inherited bleeding disorder caused by an abnormality in the F8 gene that leads to a reduction in clotting factor VIII (FVIII). Females who inherit the abnormal gene can pass on the gene to their children and are known as ‘carriers’. Some carriers have FVIII levels below 40% of normal levels and are classified as having hemophilia A. However, excessive bleeding can also occur in females with FVIII levels greater than 40% of normal. Excessive bleeding may only be evident after injury, during surgery or during childbirth, but can also cause heavy periods, for example. Replacement therapy with FVIII can be used to treat or prevent bleeds in people with hemophilia A. During surgery higher levels of FVIII may be needed to prevent excessive bleeding. However, information on the use of FVIII comes predominantly from trials in male patients with severe disease. Information on the treatment of carriers is limited, and treatment guidelines for surgical management of carriers are lacking. Simoctocog alfa (Nuwiq®), a FVIII therapy, is effective at preventing and treating bleeds, including during surgery, in males with severe hemophilia A. NuDIMENSION is a multicenter, international study that will evaluate simoctocog alfa in women and girls with hemophilia A who need major surgery. The study will include women/girls aged 12 years or older who have mild or moderate hemophilia A and who are planned to have a major surgery. The primary endpoint is overall hemostatic efficacy (“success” or “failure”), that is, how well bleeding is prevented/controlled. This will be assessed at the end of the surgery and at the end of the postoperative period. Up to 28 women and girls will take part in the study. Data from NuDIMENSION will provide important information to help decide how best to treat women/girls with hemophilia A who need surgery.
© The Author(s), 2024.