# Reduced Volume and Faster Infusion Rate of Activated Prothrombin Complex Concentrate: A Phase 3b/4 Trial in Adults with Hemophilia A with Inhibitors

## TL;DR

A clinical trial found that a blood clotting treatment for hemophilia patients with inhibitors was safe when given in smaller volumes and faster infusion rates.

## Contribution

Demonstrated the safety of reduced-volume and faster-infusion aPCC in hemophilia A patients with inhibitors.

## Key findings

- Reduced-volume aPCC infusions had similar safety profiles to standard regimens.
- Faster infusion rates up to 10 U/kg/min did not increase adverse events significantly.
- No thromboembolic events were observed in the study.

## Abstract

Background
 Activated prothrombin complex concentrate (aPCC) is indicated for bleed treatment and prevention in patients with hemophilia with inhibitors. The safety and tolerability of intravenous aPCC at a reduced volume and faster infusion rates were evaluated.

Methods
 This multicenter, open-label trial (NCT02764489) enrolled adults with hemophilia A with inhibitors. In part 1, patients were randomized to receive three infusions of aPCC (85 ± 15 U/kg) at 2 U/kg/min (the approved standard rate at the time of the study), in a regular or 50% reduced volume, and were then crossed over to receive three infusions in the alternative volume. In part 2, patients received three sequential infusions of aPCC in a 50% reduced volume at 4 U/kg/min and then at 10 U/kg/min. Primary outcome measures included the incidence of adverse events (AEs), allergic-type hypersensitivity reactions (AHRs), infusion-site reactions (ISRs), and thromboembolic events.

Results
 Of the 45 patients enrolled, 33 received aPCC in part 1 and 30 in part 2. In part 1, 24.2 and 23.3% of patients with regular and reduced volumes experienced AEs, respectively; 11 AEs in eight patients were treatment related. AHRs and ISRs occurred in four (12.1%) and two (6.1%) patients, respectively. In part 2, 3.3 and 14.3% of patients with infusion rates of 4 and 10 U/kg/min experienced AEs, respectively; only one AE in one patient was treatment related; no AHRs or ISRs were reported. Most AEs were mild/moderate in severity. Overall, no thromboembolic events were reported.

Conclusions
 aPCC was well tolerated at a reduced volume and faster infusion rates, with safety profiles comparable to the approved regimen.