Kcentra (plasma-derived prothrombin complex concentrate) / CSL Behring - LARVOL DELTA

Successful Urgent Liver Transplantation in a High-Risk Patient on Therapeutic Apixaban: A Complex Case of End-Stage Liver Disease and Hepatocellular Carcinoma with Portal Vein Thrombosis (IARS-SOCCA 2025) - "Their suggestion was low molecular weight heparin as first line and vitamin K antagonists (Warfarin) be used as second line...Given apixaban use and the patient's ESLD and CKD3b, a multidisciplinary team discussed apixaban reversal with anti-inhibitor coagulant complex (FEIBA) vs prothrombin complex concentrate [human] (Kcentra); our institution has removed the FDA approved reversal agent for Xa inhibitors (recombinant Factor Xa) from formulary...Once the portal clamp was removed, one gram of tranexamic acid was administered...This case highlights the complexities of managing therapeutic anticoagulation with apixaban in urgent LT. Patients with ESLD are at high risk for any major surgery due to significant coagulopathy; however, in the setting of liver transplantation, a fine balance exists. In the prehepatic and anhepatic phases, it is important to minimize blood loss from the surgical perspective as well as adequately resuscitate without exacerbating venous..."

Clinical • Anesthesia • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hepatitis C • Hepatocellular Cancer • Hepatology • Hypertension • Hypotension • Infectious Disease • Ischemic stroke • Nephrology • Oncology • Solid Tumor • Thrombosis • Transplantation • Venous Thromboembolism

Post Marketing Observational Study on Safety of BALFAXAR vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure (clinicaltrials.gov) - P=N/A | N=3574 | Recruiting | Sponsor: Octapharma | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2024 ➔ Jan 2025

Enrollment open • Trial initiation date

EFFICACY AND SAFETY OF HIGH-DOSE FOUR-FACTOR PROTHROMBIN COMPLEX CONCENTRATE: LEX-209 SUBANALYSIS (SCCM 2025) - P3 | "Introduction: The LEX-209 Phase 3 randomized controlled trial of investigational four-factor prothrombin complex concentrate (4F-PCC; Octaplex®/Balfaxar®, Octapharma) demonstrated hemostatic non-inferiority to the FDA-approved control 4F-PCC (Beriplex®/Kcentra®, CSL Behring) in rapid vitamin K antagonist (VKA) reversal before urgent surgery (p< 0.001). Investigational 4F-PCC, administered at the maximum permitted dose, appeared to be safe and effective for rapid VKA reversal in urgent surgery patients with significant bleeding risk. These findings further support the use of high-dose 4F-PCC for surgical patients needing rapid VKA reversal."

Clinical • Hematological Disorders

RARE CASE OF ACQUIRED CLOTTING FACTOR INHIBITOR FROM BLADDER CANCER (SCCM 2025) - "He received 7units of FFP, 2PRBC, Vitamin-K and KCENTRA over the first few days but hematuria and coagulopathy did not improve...He was started on steroids and Factor eight inhibitor bypass activity (FEIBA) treatment for ACFI...Treatment is 3 prong; 1) correct coagulopathy 2) replenish blood loss 3) stabilize/treat immune dyscrasia. Factor V inhibitors are rare but may arise from exposure to topical fibrin glues or bovine thrombin preparations that contain bovine factor V. Early recognition, confirmation and therapy initiation of ACFI is key to ensuring positive outcome and to avoid complications from life threatening bleed"

Clinical • Bladder Cancer • Cardiovascular • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Lung Cancer • Mood Disorders • Oncology • Rheumatology • Solid Tumor • Urology

COMPARISON OF TWO DIFFERENT FIXED-DOSE FACTOR EIGHT INHIBITOR BYPASSING ACTIVITY (FEIBA) REGIMENS IN THE MANAGEMENT OF WARFARIN-ASSOCIATED COAGULOPATHIES. (WRMC 2025) - "Kcentra is the only FDA approved PCC for managing warfarin associated coagulopathies, but Factor VIII Inhibitor Bypass Activity (FEIBA) is commonly used in its place. Conclusions Our new FEIBA dosing recommendations resulted in more individuals achieving the post-FEIBA administration INR goal. Authors plan to finalize data collection and analysis in the coming months."

Cardiovascular

Rapido: Results from a UK-Wide Audit of 2477 Patients Who Received a Reversal Agent for a Direct Oral Anticoagulant (ASH 2024) - "Although a specific reversal agent for dabigatran, idarucizumab, was approved for use in the UK in 2016, the predominant option for patients taking apixaban, edoxaban, and rivaroxaban has until recently been off-licence prothrombin complex concentrate (PCC). Importantly, the data highlight delays in identification and treatment of bleeds. Further, detailed analysis of this rich dataset is on-going, and a propensity score-matched analysis of patients with GI hemorrhage will be performed to compare outcomes in patients treated with andexanet alfa, Beriplex and Octaplex."

Clinical • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Gastrointestinal Disorder • Hematological Disorders • Venous Thromboembolism

Evaluation of Fixed Dosing vs Weight Based Dosing of Kcentra in Intracranial Hemorrhage caused FactorXaInhibitors (ASHP 2024) - No abstract available

Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Evaluation of Four Factor Prothrombin Complex Kcentra Use at a Tertiary Care Medical Center (ASHP 2024) - No abstract available

Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival ( TAP Study ) (clinicaltrials.gov) - P3 | N=1370 | Terminated | Sponsor: CSL Behring | N=8000 ➔ 1370 | Trial completion date: Sep 2026 ➔ Oct 2024 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Oct 2024; Study terminated due to business reasons and slow enrollment. No safety issues were found.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination

Addition of PCC Does Not Improve the Performance of rTEG or ACT in the Measurement of Dabigatran Concentration. (ASA 2024) - "This was repeated with the addition of 1 unit/mL of PCC (KCentra, CSL Behring, Kong of Prussia, PA) to each sample. The addition of prothrombotic precursors did not improve the accuracy of either test in the determination of concentration of dabigatran. ACT or rTEG may be useful POCTs for use with dabigatran anticoagulation for CPB"

Atrial Fibrillation • Cardiovascular • Hematological Disorders • Thrombosis

SPONTANEOUS RETROPHARYNGEAL HEMATOMA WITH THE USE OF APIXABAN (CHEST 2024) - "Given his positive history of Apixaban use, IV Decadron and Kcentra were administered...While most cases of RPHs have been associated with traumatic injuries, spontaneous cases have also been reported especially in patients on warfarin and rarely on rivaroxaban... Patients developing spontaneous RPH on warfarin are often switched to direct oral anticoagulants (DOAC). However, reinitiation of anticoagulation in patients with spontaneous RPH due to DOACs remains a challenge due to rare occurrence and hence limited literature."

Atrial Fibrillation • Cardiovascular • Endocrine Disorders • Gastrointestinal Disorder • Hypertension • Obstructive Sleep Apnea • Otorhinolaryngology • Pain • Pulmonary Disease • Respiratory Diseases • Sleep Disorder

Long-Term Safety of a Four-Factor Prothrombin Complex Concentrate (Kcentra®/Beriplex® P/N): An Updated Pharmacovigilance Review. (PubMed, Thromb Haemost) - " Analysis of postmarketing pharmacovigilance safety reports demonstrated that treatment with 4F-PCC was associated with few ADRs and a low rate of TEEs across multiple indications and settings, thus confirming a positive safety profile of 4F-PCC."

Adverse events • Journal • Review • Cardiovascular • Hematological Disorders • Immunology • Thrombosis

Interactive Media-Based Approach for an Exception From Informed Consent Trial Involving Patients With Trauma. (PubMed, JAMA Surg) - "Four opt-out requests were received. The interactive media-based approach to CC and PD for the ongoing TAP trial showed the feasibility and benefits of executing an efficient, coordinated, centrally run series of locally branded and geographically targeted CC and PD campaigns for a large EFIC study."

Journal

Prethrombin-1 as a Drug Substance Promoting Hemostasis with Reduced Risk of Thrombosis. (PubMed, Thromb Haemost) - " The thrombin zymogen prethrombin-1 promotes hemostasis with reduced risk of thrombosis. Prethrombin-1 may have potential to become a life-saving treatment for patients who bleed or are at risk of bleeding."

Journal • Cardiovascular • Hematological Disorders • Thrombosis

Post Marketing Observational Study on Safety of BALFAXAR vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure (clinicaltrials.gov) - P=N/A | N=3574 | Not yet recruiting | Sponsor: Octapharma

New trial • Surgery

Critical Hemodynamic Considerations for Adult Patients With Tetralogy of Fallot and Prior Blalock-Thomas-Taussig Shunt Surgery (ATS 2024) - "Case report: A 60-year-old male with a past medical history of TOF requiring multiple prior cardiac surgeries (Left-BT shunt; TOF repair; mechanical aortic and pulmonic valve replacement on chronic anticoagulation with warfarin) presented to the emergency department due to a several day history of black tarry stools...Given these findings, he received 5 units of packed red blood cells, a unit of fresh frozen plasma, 5 mg of vitamin K and Kcentra... This case highlights the importance of understanding the unique anatomical considerations in patients with TOF after BT shunt surgery. As a result of this procedure, a branch of the subclavian artery is connected to the pulmonary artery. Involvement of the subclavian artery for the shunt can have profound implications for hemodynamic monitoring."

Clinical • Surgery • Cardiovascular • Heart Failure

Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival ( TAP Study ) (clinicaltrials.gov) - P3 | N=8000 | Recruiting | Sponsor: CSL Behring | Trial completion date: Jan 2028 ➔ Sep 2026 | Trial primary completion date: Jan 2028 ➔ Sep 2026

Trial completion date • Trial primary completion date

Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival ( TAP Study ) (clinicaltrials.gov) - P3 | N=8000 | Recruiting | Sponsor: CSL Behring | Trial completion date: Sep 2026 ➔ Jan 2028 | Trial primary completion date: Sep 2026 ➔ Jan 2028

Trial completion date • Trial primary completion date

FIXED-DOSING OF 4-FACTOR PROTHROMBIN COMPLEX CONCENTRATE FOR REVERSAL OF ANTICOAGULATION: EVALUATING THE EFFECTIVENESS, SAFETY, AND COST SAVINGS (THSNA 2024) - "Based on our real-world data over more than two years, fixed-dosing of 4F-PCC (Kcentra) for warfarin and DOAC hemorrhage management had significantly less cost than adjusted dose and is associated with similar rates of thrombosis and death compared to other studies."

Clinical • HEOR • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Venous Thromboembolism

EARLY CHOLESTASIS AND VITAMIN K DEFICIENCY PRESENTING AS COAGULOPATHY AND THYMIC HEMORRHAGE (ASPHO 2024) - "Infant received 2 mg vitamin K for three days, 50 IU/kg KCentra, and 15 mg/kg fresh frozen plasma... Bleeding associated with Vitamin K deficiency and cholestasis may present variably in neonates, including intracranial bleeding, bruising, and coagulopathy; in this case, our patient presented with thymic bleeding and mediastinal mass. Vitamin K deficiency is correctable in the acute setting, however, early identification and further evaluation is indicated to address underlying causes of cholestasis."

Cholestasis • Hematological Disorders • Hepatology

An investigational four-factor prothrombin complex concentrate for vitamin k antagonist reversal: hemostatic efficacy and safety demonstrated with and without concurrent vitamin k therapy (ISICEM 2024) - "LEX -209 was a Phase 3 non -inferiority randomized control trial of an investigational 4F -PCC (Octaplex®, Octapharma), which demonstrated hemostatic non -inferiority to the FDA-approved control 4F -PCC (Kcentra®, CSL Behring) in rapid vitamin K antagonist (VKA) reversal before urgent surgery (P<0.001). Investigational 4F -PCC was hemostatically non -inferior to control 4F -PCC for rapid VKA reversal in patients requiring urgent surgery with significant bleeding risk, regardless of concomitant vitamin K therapy. These findings support consideration of investigational 4F -PCC as a therapeutic option for surgical patients requiring rapid VKA reversal."

Clinical • Hematological Disorders

Balfaxar: Another four-factor PCC for warfarin reversal. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal

Twenty Years of 4-Factor Prothrombin Complex Concentrate: Review and Advances of Octaplex/Balfaxar (SCCM 2024) - "In a head-to-head Phase III randomized double-blind study (n=208), Octaplex®/Balfaxar® was non-inferior to control 4F-PCC (Kcentra®, CSL Behring) in achieving hemostatic efficacy with similar INR correction and safety profiles. Multiple clinical studies have shown that Octaplex®/Balfaxar® is an effective hemostatic agent for various indications including VKA reversal, with a favorable safety profile. Ongoing studies are expanding the role of 4F-PCC."

Review • Cardiovascular

OPSTAHT: Administration of Prothrombin Complex Concentrate vs. Standard Transfusion During/After Heart Transplantation (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Kathirvel Subramaniam | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Cardiovascular • Heart Failure • Transplantation

Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival ( TAP Study ) (clinicaltrials.gov) - P3 | N=8000 | Recruiting | Sponsor: CSL Behring

Trial completion date • Trial primary completion date