Real-World Experience with a New Human Fibrinogen Concentrate (Fibryga®) in France for the Treatment of Bleeding Episodes and Surgical Prophylaxis

Introduction: Fibrinogen deficiency can be either congenital, or acquired due to situations such as trauma, excessive surgical bleeding, or post-partum hemorrhage (PPH). Transfusion of human fibrinogen concentrate (HFC) can correct this deficiency, preventing hemorrhage and excessive blood loss. This study aimed to describe the use of a new, highly purified HFC (Fibryga®; Octapharma) recently granted temporary import authorization for use in congenital and acquired fibrinogen deficiencies in France.

Methods: This observational, non-interventional, retrospective database study was conducted in five French hospitals, according to French regulations and data protection laws. Data was retrieved from the medical files of patients with fibrinogen deficiency who received the new HFC from December 2017 to July 2019. Indication, modality, efficacy and safety outcomes were recorded. Success for treatment of bleeding episodes was defined as control of bleeding or hemoglobin loss <20%. In surgical prophylaxis, treatment success was defined as the absence of major perioperative hemorrhage, according to hospital records.

Results: The interim analysis included 110 patients with a mean (±SD) age of 56.9 (±17.7) years. All patients presented with acquired fibrinogen deficiency requiring administration of HFC, with indications and doses shown in Table 1. Treatment success rates were 88.4% (95% Confidence Interval [CI]: 78.8–98.0%) for non-surgical bleeding, 96.8% (95% CI 90.6–100%) for surgical bleeding (SB) and 91.2% (95% CI 81.6–100%) for surgical prophylaxis. Overall tolerance was good.

Subgroup analyses were performed for patients undergoing cardiac surgery and those with PPH.

Cardiac Surgery

In total, 52 patients underwent cardiac surgery (aortic dissection repair, aortic surgery, cardiac valvuloplasty, coronary bypass, complex aortic surgery or heart transplantation). Patients were aged 64.9 ± 12.3 years and 69% were male. Indications were SB (n=26, 50%) and prevention of SB (n=26, 50%). Mean total doses of HFC were 1.85 ± 0.97 g for SB and 2.27 ± 1.37 g for prevention of SB. Success rates were 100% (95% CI 100–100%] and 92.3% [95% CI 82.1–100%] respectively.

In a subset of pediatric patients (n=17), aged between 4 days and 6 years (with the exception of two who were 17) patients received on-demand HFC for bleeding prevention prior to cardiac surgery. Mean total dose of HFC was lower than in the full population (0.74 ± 0.58 g) with a mean of 1.06 ± 0.43 doses per patient. Two patients received more than one dose, with a mean of 0.65 ± 0.82 hours between doses. The success rate for bleeding prevention was 94.12% (95% CI: 82.93-100.00%]. No patients reported a hemoglobin variation of <20%. One patient received a red blood cell transfusion prior to HFC treatment, and no patients required transfusions following HFC.

PPH

A total of 44 (40.0%) patients in the interim analysis were female. Of these, 29 (65.9%) were not pregnant and 15 (34.1%) were post-partum and presented with PPH. Mean age for the PPH patients was 32.8 (±4.9) years, and mean weight 84.67 (±19.58) kg. For women with PPH (N=15), the mean total dose of HFC was 2.53 ± 0.74 g (29.64 ± 9.68 mg/kg) with mean number of doses of 1.33 ± 0.72. Time between first and second dose was 2.88 ± 3.63 hours. The treatment success rate for PPH patients was and 86.7% (95% CI: 69.5–100%) for PPH with bleeding control achieved for 9 (60.0%) with a mean blood loss of 1.87 (±0.88) L. A total of 11 (73.3%) PPH patients required transfusions, 8 (72.7%) before HFC and 3 following HFC. Overall, tolerance was good for all patients with no adverse drug reactions reported.

Conclusions: In real-world practice, the new HFC was used mostly for bleeding control. In around one third of patients, HFC was administered as prophylaxis to avoid surgical bleeding. HFC was found to be effective in specific subpopulations including patients undergoing cardiac surgery and women with PPH. Use of HFC was associated with favorable efficacy outcomes and no safety concerns were identified.