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The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors
Escobar M, Castaman G, Boix SB, Callaghan M, de Moerloose P, Ducore J, Hermans C, Journeycake J, Leissinger C, Luck J, et al
Haemophilia : the official journal of the World Federation of Hemophilia. 2021
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Abstract
INTRODUCTION Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (≥12 years of age). We describe here the EB safety profile from the three prospective Phase 3 clinical trials performed to date. AIM: To assess EB safety, immunogenicity and thrombotic potential in children and adults who received EB for treatment of bleeding and perioperative care. METHODS Using a randomized crossover design, 27 subjects in PERSEPT 1 (12-54 years) and 25 subjects in PERSEPT 2 (1-11 years) treated bleeding episodes with 75 or 225 μg/kg EB initially followed by 75 μg/kg dosing at predefined intervals as determined by clinical response. Twelve PERSEPT 3 subjects (2-56 years) received an initial preoperative infusion of 75 μg/kg (minor procedures) or 200 μg/kg EB (major surgeries) with subsequent 75 μg/kg doses administered intraoperatively and post-operatively as indicated. Descriptive statistics were used for data analyses. RESULTS Sixty subjects who received 3388 EB doses in three trials were evaluated. EB was well tolerated, with no allergic, hypersensitivity, anaphylactic or thrombotic events reported and no neutralizing anti-EB antibodies detected. A death occurred during PERSEPT 3 and was determined to be unlikely related to EB treatment by the data monitoring committee. CONCLUSION Results from all three Phase 3 trials establish an excellent safety profile of EB in haemophilia A or B patients with inhibitors for treatment of bleeding and perioperative use.
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Evaluation of efficacy of Valsalva for attenuating needle puncture pain in first time nonremunerated voluntary plateletpheresis donors: A prospective, randomized controlled trial
Srivastava A, Kumar S, Agarwal A, Khetan D, Katharia R, Mishra P, Khati S, Gautam S, Sandeep K
Asian journal of transfusion science. 2021;15(1):68-74
Abstract
BACKGROUND Plateletpheresis is generally safe but may have adverse reactions. Adverse reactions can negatively influence donor recruitment and retention. Valsalva is a proven method of attenuating pain caused by venipuncture. AIMS The aim was to evaluate the efficacy of the Valsalva maneuver on the attenuation of needle pain and donor anxiety. SETTINGS AND DESIGN This prospective randomized controlled trial was conducted between November 2015 and April 2016 at the Department of Transfusion Medicine. SUBJECTS AND METHODS One-hundred and sixty consecutive donors were grouped into control group (C) and Valsalva group (V) each of sample size 80. The Valsalva group performed a Valsalva maneuver and control did nothing before the venipuncture. Anxiety and pain were scored using a 10 cm visual analog scale (VAS). Severity was graded as VAS = 0 defines no pain and anxiety, VAS = 1-3 as mild pain and anxiety, VAS = 4-6 as moderate pain and anxiety, VAS = 7-9 as severe pain and anxiety, whereas VAS = 10 denotes extreme pain and anxiety. STATISTICAL ANALYSIS Statistical Package for Social Sciences, version 23 was used for analysis. Independent samples t-test/Mann-Whitney U-test was used to compare between treatment and control group, whereas the Wilcoxon signed-rank test was used to test the difference between pre- and postobservations. RESULTS In the Valsalva group, post-Valsalva anxiety levels were significantly reduced to (1 [0-2]) from their pre-Valsalva values of (2 [0-3]); (P < 0.001). Pain was significantly lower (2[1-2]) in Valsalva group compared to control (4[2-5]); (P < 0.001). CONCLUSIONS Valsalva reduced both severity of venipuncture pain and anxiety. Valsalva can be performed by donors as it is an easy, painless, and nonpharmacological method of pain and anxiety attenuation.
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Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency
Ross C, Rangarajan S, Karimi M, Toogeh GH, Apte S, Lissitchkov T, Acharya S, Manco-Johnson MJ, Srivastava A, Brand B, et al
Journal of Thrombosis and Haemostasis : Jth. 2017;16((2):):253-261
Abstract
BACKGROUND Human fibrinogen concentrate (HFC) corrects fibrinogen deficiency in congenital a-/hypofibrinogenaemia. OBJECTIVES To assess pharmacokinetics (PK), effects on thromboelastometry maximum clot firmness (MCF), and safety of a new double virus-inactivated/eliminated, highly purified HFC vs. active control. PATIENTS/METHODS In this multinational, randomized, phase II, open-label, crossover study in 22 congenital afibrinogenaemia patients ≥12 years, 70 mg kg(-1) of new HFC (FIBRYGA, Octapharma AG) or control (Haemocomplettan((R)) P/RiaSTAP() , CSL Behring GmbH) were administered, followed by crossover to the other concentrate. Fibrinogen activity, PK and MCF in plasma were assessed. RESULTS The concentrates were not bioequivalent for the primary endpoint, AUCnorm (mean ratio 1.196; 90% CI: 1.117, 1.281). Remaining PK parameters (Cmaxnorm , IVR, t1/2 , MRT) reflected bioequivalence between concentrates, except for clearance (mean ratio 0.836; 90% CI: 0.781, 0.895) and Vss (mean ratio 0.886; 90% CI: 0.791, 0.994). Mean AUCnorm was significantly larger for the new HFC (1.62 +/- 0.45 vs. 1.38 +/- 0.47 h kg g L(-1) mg(-1) , p=0.0001) and mean clearance was significantly slower (0.665 +/- 0.197 vs. 0.804 +/- 0.255 mL h(-1) kg(-1) , p=0.0002). Mean MCF increased from 0 mm to 9.68 mm (new HFC) and 10.00 mm (control) 1-hour post-infusion (mean difference -0.32 mm, 95% CI -1.70, 1.07, n.s.). No deaths, thromboses, viral seroconversions or serious related adverse events occurred. CONCLUSIONS Bioequivalence was not demonstrated for AUCnorm , clearance and Vss. Larger AUCnorm and slower clearance were observed for the new HFC. Remaining pharmacokinetic parameters reflected bioequivalence to control. Safety profiles and increases in clot strength were comparable between concentrates. This article is protected by copyright. All rights reserved.