PMID- 33772963
OWN - NLM
STAT- MEDLINE
DCOM- 20210924
LR  - 20210924
IS  - 1365-2516 (Electronic)
IS  - 1351-8216 (Print)
IS  - 1351-8216 (Linking)
VI  - 27
IP  - 3
DP  - 2021 May
TI  - Results of a randomized phase III/IV trial comparing intermittent bolus versus 
      continuous infusion of antihaemophilic factor (recombinant) in adults with severe 
      or moderately severe haemophilia A undergoing major orthopaedic surgery.
PG  - e331-e339
LID - 10.1111/hae.14219 [doi]
AB  - INTRODUCTION: In patients with haemophilia A undergoing surgery, factor VIII 
      (FVIII) replacement therapy by continuous infusion (CI) may offer an alternative 
      to bolus infusion (BI). AIM: To compare the perioperative haemostatic efficacy 
      and safety of antihaemophilic factor (recombinant) (ADVATE((R)) ; Baxalta US Inc., 
      a Takeda company, Lexington, MA, USA) CI or BI administration. METHODS: In this 
      multicentre, phase III/IV, controlled study (NCT00357656), 60 previously treated 
      adult patients with severe or moderately severe disease undergoing elective 
      unilateral major orthopaedic surgery (knee replacement, n = 48; hip surgery, 
      n = 4; other, n = 8) requiring drain placement were randomized to receive 
      antihaemophilic factor (recombinant) CI (n = 29) or BI (n = 31) through 
      postoperative day 7. Primary outcome measure was cumulative packed red blood cell 
      (PRBC)/blood volume in the drainage fluid within 24 h after surgery, used to 
      establish non-inferiority of CI to BI. RESULTS: CI:BI ratio of cumulative PRBC 
      volume in the 24-h drainage fluid was 0.92 (p-value <.001 for non-inferiority; 
      95% confidence interval, 0.82-1.05). Total antihaemophilic factor (recombinant) 
      dose per kg body weight received in the combined trans- and postoperative periods 
      was similar with CI and BI to maintain targeted FVIII levels during/after 
      surgery. Treatment-related adverse events (AEs) were reported in five patients 
      treated by CI (eight events) and five treated by BI (six events), including two 
      serious AEs in each arm. CONCLUSION: CI administration of antihaemophilic factor 
      (recombinant) is a viable alternative to BI in patients with haemophilia A 
      undergoing major orthopaedic surgery, providing comparable efficacy and safety.
CI  - (c) 2021 Takeda Pharmaceuticals International AG, Zurich Switzerland. Haemophilia 
      published by John Wiley & Sons Ltd.
FAU - Pabinger, Ingrid
AU  - Pabinger I
AUID- ORCID: 0000-0002-7677-9896
AD  - Medical University of Vienna, Vienna, Austria.
FAU - Mamonov, Vasily
AU  - Mamonov V
AD  - National Research Center for Hematology, Moscow, Russia.
FAU - Windyga, Jerzy
AU  - Windyga J
AUID- ORCID: 0000-0001-7877-4784
AD  - Department of Disorders of Hemostasis and Internal Medicine, Institute of 
      Hematology and Transfusion Medicine, Warsaw, Poland.
FAU - Engl, Werner
AU  - Engl W
AD  - Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
FAU - Doralt, Jennifer
AU  - Doralt J
AD  - Baxalta Innovations GmbH, a Takeda company, Vienna, Austria.
FAU - Tangada, Srilatha
AU  - Tangada S
AD  - Baxalta US Inc., a Takeda company, Cambridge, Massachusetts, USA.
FAU - Spotts, Gerald
AU  - Spotts G
AD  - Baxalta US Inc., a Takeda company, Cambridge, Massachusetts, USA.
FAU - Ewenstein, Bruce
AU  - Ewenstein B
AD  - Baxalta US Inc., a Takeda company, Cambridge, Massachusetts, USA.
LA  - eng
GR  - Baxalta US Inc., a Takeda company, Lexington, MA, USA/
GR  - Baxalta Innovations GmbH, a Takeda company, Vienna, Austria/
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20210327
PL  - England
TA  - Haemophilia
JT  - Haemophilia : the official journal of the World Federation of Hemophilia
JID - 9442916
RN  - 0 (Recombinant Proteins)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Adult
MH  - Blood Coagulation Tests
MH  - Factor VIII/therapeutic use
MH  - *Hemophilia A/drug therapy/surgery
MH  - Hemostasis
MH  - Humans
MH  - *Orthopedic Procedures
MH  - Recombinant Proteins
PMC - PMC8252548
OTO - NOTNLM
OT  - clinical trial
OT  - haemophilia A
OT  - intravenous infusion
OT  - orthopaedic surgery
OT  - recombinant factor VIII
COIS- IP has received occasional honoraria for lectures and advisory board meetings 
      from Bayer, CSL Behring, Novo Nordisk, Pfizer, Sobi and Shire*; unrestricted 
      research grants from CSL Behring, Novo Nordisk and Shire*. VM has no conflict of 
      interest to declare. JW has received research grants/honoraria for lectures from 
      Baxalta, Bayer, CSL Behring, Ferring Pharmaceuticals, Novo Nordisk, Octapharma, 
      Pfizer, Roche, Siemens, Shire*, Sobi and Werfen. WE is an employee of Baxalta 
      Innovations GmbH, a Takeda company, and a Takeda stock owner. JD is an employee 
      of Baxalta Innovations GmbH, a Takeda company. ST and BE are employees of Baxalta 
      US Inc., a Takeda company, and Takeda stock owners. GS was an employee of Baxalta 
      US Inc., a Takeda company, at the time of the current study. *A member of the 
      Takeda group of companies.
EDAT- 2021/03/28 06:00
MHDA- 2021/09/25 06:00
PMCR- 2021/07/02
CRDT- 2021/03/27 17:37
PHST- 2020/11/04 00:00 [revised]
PHST- 2020/06/03 00:00 [received]
PHST- 2020/11/09 00:00 [accepted]
PHST- 2021/03/28 06:00 [pubmed]
PHST- 2021/09/25 06:00 [medline]
PHST- 2021/03/27 17:37 [entrez]
PHST- 2021/07/02 00:00 [pmc-release]
AID - HAE14219 [pii]
AID - 10.1111/hae.14219 [doi]
PST - ppublish
SO  - Haemophilia. 2021 May;27(3):e331-e339. doi: 10.1111/hae.14219. Epub 2021 Mar 27.