Share this page
FORMA 05 Trial
)
FORMA-05 was a single-center, prospective, randomized Phase II pilot study that investigated the haemostatic efficacy and safety of fibryga® compared to an active control (cryoprecipitate) in patients aged 18 years and older undergoing cytoreductive surgery for pseudomyxoma peritonei.
Treatment was guided by a ROTEM-based protocol.
The study included 45 patients in the full analysis set (FAS)/safety population, with 43 patients included in the per-protocol population, which served as the primary analysis group.
Primary objective
To compare the overall haemostatic efficacy of fibryga® with cryoprecipitate in bleeding patients who developed acquired fibrinogen deficiency during surgery.
Efficacy
Overall haemostatic efficacy
All patients in both the fibryga® and active control groups (per-protocol population) were deemed to have achieved treatment success for overall haemostatic efficacy, as determined by the IDMEAC.
A post-hoc analysis showed that fibryga® was non-inferior to active control for overall haemostatic efficacy (p=0.01; Farrington–Manning test).
Intra-operative haemostatic efficacy
The IDMEAC rated intra-operative efficacy as excellent or good in 95.2% of patients in the fibryga® group, compared to 72.7% in the active control group (per-protocol population).
Significantly higher increase in fibrinogen levels & in FIBTEM A20
fibryga® showed significantly greater increases compared to cryoprecipitate after each intraoperative administration.
Mean (±SD) increase in plasma fibrinogen: fibryga® 0.78 g/L (±0.34) vs. cryoprecipitate 0.35 g/L (±0.29; P < .0001)
Mean (±SD) increase in FIBTEM A20: fibryga® 3.33 mm (±1.99) vs. cryoprecipitate 0.93 mm (±2.91), (P = .003).
Quick access time
fibryga® was delivered to the operating room a mean of 46 minutes earlier than cryoprecipitate. Consequently, the mean time from randomization to the start of the initial infusion was reduced by 24 minutes for the fibryga® group (p<0.0001).
Table 1: Intraoperative haemostatic efficacy ratings assessed by the IDMEAC.
Safety
There were 225 AEs in 22 patients in the fibryga® group and 228 AEs in 23 patients in the cryoprecipitate group (safety population) (Figure 1). There were 6 SAEs in the fibryga® group and 17 SAEs in the active control group.
No thromboembolic events were observed with fibryga®; however, seven patients (30.4%) in the cryoprecipitate group experienced seven thromboembolic events (five pulmonary embolism events and two deep vein thrombosis events).
There was one AE (gastrointestinal anastomotic leak) leading to discontinuation and death in one patient in the active control group; this was deemed unrelated to study drug.
Figure 1: Number of Adverse Events
Reference
Roy A, Stanford S, Nunn S, Alves S, Sargant N, Rangarajan S, Smith EA, Bell J, Dayal S, Cecil T, Tzivanakis A, Kruzhkova I, Solomon C, Knaub S, Moran B, Mohamed F. Efficacy of fibrinogen concentrate in major abdominal surgery - A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei. J Thromb Haemost. 2020 Feb;18(2):352-363. doi: 10.1111/jth.14665. Epub 2019 Nov 26. PMID: 31654548; PMCID: PMC7027898. [PubMed]
