Acquired Fibrinogen Deficiency
Conditions
Keywords
Fibrinogen deficiency, Pseudomyxoma peritonei, Cytoreductive surgery, Hyperthermic intraperitoneal chemotherapy, Blood coagulation disorder
Brief summary
This study is a phase 3, prospective, single center, randomized, open label, controlled, parallel arm, interventional study to investigate the efficacy and safety of CSL511, in participants undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) with predicted intraoperative blood loss of greater than or equal to (\>=) 2 liter (L). Eligible participants will be randomized in a 1:1 ratio to 1 of 2 treatment arms, to receive CSL511 or cryoprecipitate.
Interventions
BIOLOGICALCSL511 Fibrinogen concentrate (human)
CSL511 will be prepared in sterile water for injection and administered as an intravenous (IV) infusion.
BIOLOGICALCryoprecipitate
Cryoprecipitate will be administered via IV infusion.
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* • Aged \>= 18 years at the time of providing written informed consent. * • Diagnosis of PMP requiring CRS with HIPEC. * • Bleeding risk: Predicted intraoperative blood loss of \>=2L, assessed within 60 and 100 mins after start of study surgery (assessment made before 2 L of blood is lost)
Exclusion criteria
* • Confirmed or suspected congenital or acquired coagulation disorder or a prothrombotic disorder * • Myocardial infarction, acute coronary syndrome, or stroke within 2 months before study surgery. * • Known history of chronic hepatitis. * • Clopidogrel or ticagrelor administration within 5 days before study surgery. * • Prasugrel administration within 7 days before study surgery. * • Oral factor Xa inhibitor administration within 2 days before study surgery. * • Glycoprotein IIb / IIIa antagonist administration within 24 hours before study surgery. * • Oral direct thrombin inhibitor administration within 3 days before study surgery. * • Vitamin K antagonists within 5 days before study surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with overall hemostatic success | During surgery to 24 hours after surgery | Overall hemostatic success will be assessed by an independent data monitoring and efficacy adjudication committee (IDMEAC). The IDMEAC will assess the overall efficacy based on a composite of intraoperative and postoperative hemostasis using a 4-point scale, where ratings correspond to excellent or good (hemostatic success) or moderate or none (hemostatic failure). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-emergent (TE): adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) | Up to 30 days after IV infusion | The TE AESIs include thromboembolic events, viral transmission/seroconversion, and anaphylaxis and severe hypersensitivity/severe allergic reactions. |
| Number of participants with intraoperative hemostatic efficacy | During surgery | Intraoperative hemostatic efficacy will be assessed by the surgeon and anesthesiologist using an objective 4-point hemostatic efficacy scale, where ratings correspond to excellent or good (hemostatic success) or moderate or none (hemostatic failure). |
| Number of participants with postoperative hemostatic efficacy | Up to 24 hours after surgery | Postoperative hemostatic efficacy will be assessed by a hematologist using an objective 4-point hemostatic efficacy scale, where ratings correspond to excellent or good (hemostatic success) or moderate or none (hemostatic failure). |
| Plasma fibrinogen concentration | During surgery, at the end of surgery and up to 24 hours after start of surgery | — |
| Mean total dose of fibrinogen administered | During surgery, at the end of surgery and up to 24 hours after start of surgery | — |
| Number of doses of fibrinogen administered | During surgery, at the end of surgery and up to 72 hours after start of surgery | — |
| Duration of surgery | During surgery | — |
| Intraoperative blood loss | During surgery | — |
| Intraoperative requirements for blood products | During surgery | Blood products include fresh frozen plasma, red blood cells, and platelets. |
| Postoperative blood loss | Up to 48 hours after start of surgery | — |
| Postoperative requirements for blood products | Up to 9 days after surgery | Blood products include fresh frozen plasma, red blood cells, and platelets. |
| Number of participants with reoperation (for bleeding) | Up to 30 days after surgery | — |
| Number of participants with reoperation (for reasons other than bleeding) | Up to 30 days after surgery | — |
| Duration of mechanical ventilation | Up to 30 days after surgery | — |
| Duration of intensive care unit (ICU) stay | Up to 30 days after surgery | — |
| Duration of hospital stay | Up to 30 days after surgery | — |
| 21-day mortality | Up to 21 days after surgery | — |
| In-hospital mortality | Up to 30 days after surgery | — |
| Time between placing the investigational product (IP) order to administration | During surgery | The following time to event parameters will be assessed: time between when IP is ordered and when IP is ready to administer in the operating room and time between when IP is ordered and start of IP administration. |
| Prothrombin time and activated partial thromboplastin time | Up to 8 days after surgery | — |
| Coagulation factor profile | Up to 8 days after surgery | The following coagulation factor profiles will be assessed: fibrinogen, factor VIII (FVIII):C, von Willebrand ristocetin cofactor (VWF:Rco) and factor XIII (FXIII). |
| Coagulation parameter profile | Up to 8 days after surgery | The following coagulation parameter profiles will be assessed: thrombin generation marker, protein C and S, antithrombin and alpha 2-antiplasmin. |
Countries
United Kingdom
Contacts
CONTACTTrial Registration Coordinator
STUDY_DIRECTORStudy Director
CSL Behring
Outcome results
None listed