A multicentre prospective open-label study assessing efficacy and safety of a triple-secured fibrinogen concentrate in the treatment of postpartum haemorrhage

Introduction

Postpartum haemorrhage (PPH) is a major cause of global maternal morbidity and mortality. The use of haemostatic drugs in the therapeutic management of patients is mainly empirical. A rationale for an early treatment with fibrinogen, however, has been recently suggested [1].

Methods

A multicentre, noncontrolled, phase 2 study was performed to assess the efficacy and the safety of a new triple-secured fibrinogen concentrate (FGT1; LFB, Les Ulis, France) in the treatment of PPH. A single median dose of 30 mg/kg was administered in addition to standard care. Patients were followed until 6 weeks after the inclusion. Failure of treatment was defined when ultimate resources (that is, invasive hæmostatic intervention or treatment with activated recombinant factor VII) were required to stop the hæmorrhage, or in case of massive transfusion or death. Other clinical criteria included the course of haemorrhage and investigator's assessment using a four-point scale. Laboratory assessments were changes in fibrinogen plasma levels and in the FibTEM A15 parameter (RoTEM^®). Safety included adverse events and vital signs.

Results

Sixteen patients were included with a median (range) volume of haemorrhage of 1,667 (800; 3,160) ml at baseline. FGT1 succeeded in controlling the haemorrhage in 75% of the 12 patients who were clinically assessable. A convergence was observed for all efficacy criteria used. The median fibrinogen incremental recovery was 10.0 (g/l)/(g/kg) with a 7% concomitant median increase of A15 FibTEM. Biological ranges were also very large. Higher incremental recovery and relative increases of FibTEM A15 were associated with clinical success. FGT1 was well tolerated in all patients. Among the 14 adverse events reported, only one was serious, but all were reported as not related to FGT1. No thrombosis or allergic reaction to the study drug occurred.

Conclusion

This exploratory study suggests efficacy of FGT1 to control PPH in cases of failure of first-line treatments. Most severe PPH may require higher doses than used in this study. These results are to be confirmed by larger controlled trials.